WO2023086969A2

WO2023086969A2 - Treatment methods

Info

Publication number: WO2023086969A2
Application number: PCT/US2022/079767
Authority: WO
Inventors: Hanna S. STAROBINETS; Victoria L. DEVAULT; Hubert LAM; Tulin DADALI-ABEL; Jessica Baker Flechtner
Original assignee: Ichor Medical Systems Inc.
Priority date: 2021-11-12
Filing date: 2022-11-11
Publication date: 2023-05-19
Also published as: WO2023086969A3

Abstract

Methods and compositions for identifying antigens of human lymphocytes, and for treating subjects having an autoimmune disease, are provided herein.

Description

TREATMENT METHODS

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/328,532, filed April 07, 2022, and U.S. Provisional Application No. 63/278,844, filed November 12, 2021, the contents of each of which are hereby incorporated by reference herein in their entirety.

BACKGROUND

[0002] Autoimmune disease develops when the body’s immune system attacks its own healthy cells. There are various types of autoimmune diseases, for instance, Type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, pre-eclampsia, multiple sclerosis, and vasculitis. Development of autoimmune diseases includes two general components: (i) a loss of tolerance to self-antigens, and (ii) immune-mediated injury of healthy cells. The National Institutes of Health (NIH) estimates that as many as 23.5 million Americans suffer from an autoimmune disease. (NIH The Autoimmune Diseases Coordinating Committee_2005). Moreover, prevalence of autoimmune diseases is rising. Thus, there exists a continuing unmet need for improved methods to treat autoimmune diseases and overactive immune conditions.

SUMMARY

[0003] The present disclosure features, inter alia, compositions and methods for inhibiting or decreasing an immune response in a subject.

[0004] One aspect of the disclosure includes a vaccine for inhibiting or decreasing an immune response in a subject with an autoimmune disease comprising an inhibigen and an effective amount of an adjuvant. In some embodiments, the inhibigen is a peptide. In some embodiments, the peptide is encoded by a nucleic acid. In some embodiments, the nucleic acid is a vector. In some embodiments, the nucleic acid is an RNA, optionally wherein the RNA is an mRNA. In some embodiments, the inhibigen is obtained by a method comprising: a) providing a plurality of bacterial cells or beads, wherein each bacterial cell or bead comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with human antigen presenting cells (APCs); c) contacting the APCs with a plurality of human lymphocytes; e) identifying one or more polypeptides that inhibit and/or suppress cytolytic T cell activity; and f) selecting one or more inhibitory polypeptides; thereby selecting the inhibigen. In some embodiments, the method further comprises contacting the APCs with the adjuvant.

[0005] In some embodiments, a method of attenuating or decreasing and immune response in a subject with an autoimmune disease is provided, comprising: administering the vaccine to the subject. In some embodiments, the administration of the vaccine results in a decreased IFNy cytokine production by the immune cells of the subject. In some embodiments, the vaccine reduces or abolishes cytolytic T cell activity. In some embodiments, the autoimmune disease is multiple sclerosis.

[0006] One aspect of the disclosure includes a method of inhibiting or decreasing an immune response in a subject, comprising a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises human antigen presenting cells (APCs) that internalize the bacterial cells or beads; c) contacting the first plurality of human cells with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a heterologous polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on a level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; f) selecting as one or more inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; and g) administering to the subject an immunogenic composition comprising one or more of the selected antigens or immunogenic fragment thereof, thereby inhibiting or decreasing, relative to a control, an immune response in the subject.

[0007] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, the first and second plurality of human cells come from different donors. In some embodiments, at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

[0008] In some embodiments, the subject is susceptible to or is suffering from an autoimmune disease or overactive immune condition.

[0009] In another aspect, the disclosure features a method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises human antigen presenting cells (APCs) that internalize the bacterial cells or beads; c) contacting the first plurality of human cells with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a heterologous polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on a level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; f) selecting as one or more inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; and g) administering to the subject an immunogenic composition comprising one or more of the selected antigens or immunogenic fragments thereof, thereby treating the autoimmune disease or overactive immune condition.

[0010] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, the first and second plurality of human cells come from different donors. In some embodiments, at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

[0011] Another aspect of the disclosure includes a method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; restimulating the expanded, selectively stimulated lymphocytes with the plurality of overlapping peptides; and administering the expanded, selectively stimulated lymphocytes (e.g., T cells) to the subject, thereby treating the autoimmune disease or overactive immune condition.

[0012] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, the first and second plurality of human cells come from different donors. In some embodiments, at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors. In some embodiments, the one or more additional donors are susceptible to or are suffering from an autoimmune disease or overactive immune condition.

[0013] In some embodiments, the method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers. In some embodiments, the method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

[0014] Another aspect of the disclosure includes a method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; and administering the expanded, selectively stimulated lymphocytes (e.g., T cells) to the subject, thereby treating the autoimmune disease or overactive immune condition.

[0015] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, wherein the first and second plurality of human cells come from different donors. In some embodiments, at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors. In some embodiments, the one or more additional donors are susceptible to or are suffering from an autoimmune disease or overactive immune condition.

[0016] In some embodiments, the method does not comprise a further step of restimulating the selectively stimulated lymphocytes (e.g., by the one or more of the overlapping peptides). In some embodiments, the method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers. In some embodiments, the method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

[0017] Another aspect of the disclosure includes A pharmaceutical composition comprising a plurality of selectively stimulated lymphocytes, wherein the selectively stimulated lymphocytes are obtained by a method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; restimulating the expanded, selectively stimulated lymphocytes with the plurality of overlapping peptides; and formulating the restimulated, expanded, selectively stimulated lymphocytes (e.g., T cells) from the subject as a pharmaceutical composition.

[0018] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, the first and second plurality of human cells come from different donors. In some embodiments, at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

[0019] In some embodiments, the selectively stimulated lymphocytes are obtained by a method that does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers. In some embodiments, the selectively stimulated lymphocytes are obtained by a method that does not comprise a further step of expanding the lymphocytes (e.g., T cells).

[0020] Another aspect of the disclosure includes a pharmaceutical composition comprising a plurality of selectively stimulated lymphocytes, wherein the selectively stimulated lymphocytes are obtained by a method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; and formulating the expanded, selectively stimulated lymphocytes (e.g., T cells) as a pharmaceutical composition.

[0021] In some embodiments, the first and second plurality of human cells come from the same donor. In some embodiments, the donor is the subject. In some embodiments, wherein the first and second plurality of human cells come from different donors. In some embodiments, wherein at least one donor is the subject. In some embodiments, steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

[0022] In some embodiments, the selectively stimulated lymphocytes are obtained by a method that does not comprise a further step of restimulating the selectively stimulated lymphocytes (e.g., by the one or more of the overlapping peptides). In some embodiments, the selectively stimulated lymphocytes are obtained by a method that does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers. In some embodiments, the selectively stimulated lymphocytes are obtained by a method that does not comprise a further step of expanding the lymphocytes (e.g., T cells). In some embodiments, the population of lymphocytes (e.g., T cells) comprises CD4+ and/or CD8+ T cells.

[0023] In some embodiments, the heterologous polypeptides are derived from a cancer or tumor cell, and the antigens selected are tumor antigens. In some embodiments, the tumor antigens comprise full-length polypeptides encoding mutations, splice variants, or translocations present in a cancer or tumor. In some embodiments, the tumor antigens comprise polypeptides that are fragments of full-length polypeptides encoding mutations, splice variants, or translocations present in a cancer or tumor.

[0024] In some embodiments, the heterologous polypeptides are derived from a human cell or tissue that is a target of an autoimmune response, and the antigens selected are autoimmune antigens. In some embodiments, the heterologous polypeptides are derived from a healthy human cell or tissue. [0025] In some embodiments, the antigens selected are autoantigens. In some embodiments, the heterologous polypeptides are derived from an infectious agent, and the antigens selected are antigens of the infectious agent.

[0026] In some embodiments, the selected inhibitory antigens comprise a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more inhibitory antigens. In some embodiments, the library of different heterologous polypeptides comprises at least 1, 3, 5, 10, 15, 20, 25, 30, 50, 100, 150, 250, 500, 750, 1000 or more different heterologous polypeptides, or portions thereof.

[0027] In some embodiments, determining whether one or more lymphocytes are inhibited and/or suppressed by one or more antigens comprises measuring a level of one or more immune mediators. In some embodiments, the one or more immune mediators are selected from the group consisting of cytokines, soluble mediators, and cell surface markers expressed by the lymphocytes. [0028] In some embodiments, the one or more immune mediators are cytokines. In some embodiments, the one or more cytokines are selected from the group consisting of TRAIL, IFN- gamma, IL-12p70, IL-2, TNF-alpha, MIP1 -alpha, MIPl-beta, CXCL9, CXCL10, MCP1, RANTES, IL-1 beta, IL-4, IL-6, IL-8, IL-9, IL-10, IL-13, IL-15, CXCL11, IL-3, IL-5, IL-17, IL-18, IL-21, IL- 22, IL-23 A, IL-24, IL-27, IL-31, IL-32, TGF-beta, CSF, GM-CSF, TRANCE (also known as RANK L), MIP3 -alpha, and fractalkine.

[0029] In some embodiments, the one or more immune mediators are soluble mediators. In some embodiments, the one or more soluble mediators are selected from the group consisting of granzyme A, granzyme B, sFas, sFasL, perforin, and granulysin.

[0030] In some embodiments, the one or more immune mediators are cell surface markers. In some embodiments, the one or more cell surface markers are selected from the group consisting of CD107a, CD107b, CD25, CD69, CD45RA, CD45RO, CD137 (4-1BB), CD44, CD62L, CD27, CCR7, CD154 (CD40L), KLRG-1, CD71, HLA-DR, CD122 (IL-2RB), CD28, IL7Ra (CD127), CD38, CD26, CD134 (OX-40), CTLA-4 (CD152), LAG-3, TIM-3 (CD366), CD39, PD1 (CD279), FoxP3, TIGIT, CD 160, BTLA, 2B4 (CD244), and KLRG1.

[0031] In some embodiments, the lymphocytes comprise CD4⁺ T cells. In some embodiments, the lymphocytes comprise CD8⁺ T cells. [0032] In some embodiments, lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 20%, 40%, 60%, 80%, 100%, 120%, 140%, 160%, 180%, or 200% higher or lower than a control level. In some embodiments, lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 1, 2, or 3 standard deviations greater or lower than the mean of a control level. In some embodiments, lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 1, 2, 3, 4 or 5 median absolute deviations (MADs) greater or lower than a median response level to a control.

[0033] In some embodiments, the autoimmune disease or overactive immune condition comprises an inflammatory autoimmune disease or disorder associated with an arthritis condition, a multiple sclerosis condition, an intestinal inflammatory condition, vasculitis, asthma, or transplant rejection or graft versus host disease.

[0034] In some embodiments, the methods further comprise administering to the subject a second therapy or combination of therapies for treatment of the autoimmune disease or overactive immune condition.

[0035] In some embodiments, the immune response inhibited or decreased comprises a humoral response and/or a cellular response.

[0036] In some embodiments, the selected inhibitory antigens comprise (i) an antigen described herein (e.g., comprising an amino acid sequence described herein), (ii) a polypeptide having an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence of an antigen described herein, and/or (iii) a polypeptide comprising the amino acid sequence of an antigen described herein having at least one deletion, insertion, and/or translocation. [0037] In some embodiments, the immunogenic composition or adoptive cell therapy administered to the subject decreases markers of inflammation, T cell activation aberrantly directed to autoantigens, and/or cytotoxicity in a lymphocyte from the subject. In some embodiments, the immunogenic composition administered to the subject decreases expression of markers associated with inflammation, T cell activation aberrantly directed to autoantigens, and/or cytotoxicity in a lymphocyte from the subject. In some embodiments, the immunogenic composition administered to the subject decreases IFNy secretion in a lymphocyte from the subject. In some embodiments, the immunogenic composition administered to the subject decreases T cell receptor expression in a lymphocyte from the subject. In some embodiments, the immunogenic composition administered to the subject increases markers associated with dampening of immune responses or T cell exhaustion.

[0038] In some embodiments, the immunogenic composition or adoptive cell therapy administered to the subject increases expression of markers associated with dampening of immune responses or T cell exhaustion. In some embodiments, the markers associated with dampening of immune responses or T cell exhaustion comprise PD1, LAG-3, TIM-3, CD43, CD44, CD69, CD160, BLIMP- 1, CTLA-4, 2B4/CD244/SLAMF4, or TIGIT.

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The present teachings described herein will be more fully understood from the following description of various illustrative embodiments, when read together with the accompanying drawings. It should be understood that the drawings described below are for illustration purposes only and are not intended to limit the scope of the present teachings in any way.

[0040] Figure 1 is a graph showing normalized CD8⁺ T cell response levels, measured by production of either IFNy (panel A) or TNFoc (panel B), against different mutated tumor proteins.

[0041] Figure 2 is a Venn diagram showing limited overlap between CD8⁺ T cell stimulatory and inhibitory antigens identified using methods of the disclosure compared to epitope prediction algorithms.

[0042] Figure 3 shows a diagram of exemplary methods used to rank stimulatory and inhibitory antigens of the disclosure. Three screens were run measuring IFNy and TNFoc (panel A) and a ranked list was generated based on the three screens (panels B and C).

[0043] Figure 4 is a graph showing the results of an IFNy ELISpot assay for determining the immunogenicity and level of T cell activation in response to immunization with the indicated pools of three or four antigens. Panel (A) shows the level of T cell activation in response to the indicated pools of three or four antigens administered with triple adjuvant A (CpG, 3D-PHAD, synthetic saponin). Panel (B) shows the level of T cell activation in response to the indicated pools of three or four antigens without adjuvant. Symbols represent responses from individual mice.

[0044] Figure 5 is a graph showing mean tumor areas measured over time in mice immunized with the indicated pools of four antigens.

[0045] Figure 6 shows multiple graphs of the tumor area (mm²) measured over time in individual mice of the indicated immunization groups. Panel (A) represents the tumor area in mice immunized with control PBS/DMSO only, panel (B) represents the tumor area in mice immunized with a pool of four stimulatory antigens, panel (C) represents the tumor area in mice immunized with a first pool of four inhibitory antigens, and panel (D) represents the tumor area in mice immunized with a second pool of four inhibitory antigens.

[0046] Figure 7 is a graph showing mean tumor area measured over time in mice immunized with the indicated pools of three or four antigens and triple adjuvant A (CpG, 3D-PHAD, synthetic saponin). [0047] Figure 8 shows multiple graphs of the tumor area (mm²) measured over time in individual mice of the indicated immunization groups. Panel (A) represents the tumor area in control mice immunized with adjuvant only, panel (B) represents the tumor area in mice immunized with a pool of four stimulatory antigens and adjuvant, panel (C) represents the tumor area in mice immunized with a first pool of four inhibitory antigens and adjuvant, panel (D) represents the tumor area in mice immunized with a second pool of four stimulatory antigens and adjuvant, and panel (E) represents the tumor area in mice immunized with a pool of three previously known efficacious antigens (Published) and adjuvant. Adjuvant in all cases was triple adjuvant A (CpG, 3D-PHAD, synthetic saponin).

[0048] Figure 9 shows multiple graphs of the percent survival of immunized mice over time. Panel (A) shows the percent survival of mice over time in experiments testing immunization with indicated pools of four antigens, or control PBS/DMSO only. Panel (B) shows the percent survival of mice over time in experiments testing immunization with indicated pools of three or four antigens plus triple adjuvant A (CpG, 3D-PHAD, synthetic saponin), or triple adjuvant A only.

[0049] Figure 10 shows fluorescence scans of representative tumor sections from mice immunized with phosphate buffered saline (PBS) only, or a pool of inhibitory antigens only. Panel (A) shows a fluorescent CD8⁺ and DAPI stained section of a representative (average) tumor from a mouse immunized with PBS only. Panel (B) shows a fluorescent CD8⁺ and DAPI stained section of a hyper-progressive tumor from a mouse immunized with a pool of inhibitory antigens only.

[0050] Figure 11 is a graph showing mean number of infiltrating CD8⁺ T cells in whole tumors (N=2) from mice immunized with phosphate buffered saline (PBS) only, or a pool of inhibitory antigens only.

[0051] Figure 12 shows graphs of the mean tumor volume (mm³) measured over time in mice of the indicated immunization groups. Panel (A) represents the mean tumor volume for mice immunized with: (1) adjuvant only; (2) a pool comprising inhibitory antigen In21 and two previously known efficacious antigens with adjuvant (ln21 + Published); or (3) two previously known efficacious antigens only (Published). Panel (B) represents the mean tumor volume for mice immunized as in Panel A, and additionally for mice immunized with: (4) a pool comprising 4 inhibitory antigens and two previously known efficacious antigens with adjuvant (Inhib Pool + Published); or (5) a pool comprising inhibitory antigen In 17 and two previously known efficacious antigens with adjuvant (lnl7 + Published). Adjuvant in all cases was triple adjuvant B (CpG, 3D-PHAD, QS21).

[0052] Figure 13 shows results of therapeutic immunization with a pool of 4 inhibitory antigens combined with triple adjuvant B (CpG, 3D-PHAD, QS21) compared to immunization with the adjuvant only. Results for Panels A-B are expressed as tumor volume in mm³ over time. Panel A shows mean curves for the two immunization groups. Panel B shows curves for individual mice in the two immunization groups. Panels C and D show the correlation between tumor volume in mm³ and IFNy spot forming units per 200K cells, a measure of immunogenicity and T cell activation, using two different graphing conventions. In Panel C, square symbols represent IFNy spot forming units per 200K cells. Circles represent tumor volume (mm³) on day 17, following injection with B16F10 cancer cells on day 0. Each symbol on the graphs represents the response of an individual mouse.

[0053] Figure 14 shows results of IFNy ELISpot assays for determining the immunogenicity and level of T cell activation in peripheral blood cells of mice immunized with a pool of four inhibitory antigens in combination with the indicated adjuvant. Panel (A) shows T cell activation following immunization with inhibitory antigens and poly-IC adjuvant. Panel (B) shows T cell activation following immunization with inhibitory antigens and triple adjuvant B (Triple: CpG, 3D-PHAD, QS21). Panel (C) shows T cell activation following immunization with inhibitory antigens and incomplete Freund’s adjuvant (IFA). Panel (D) shows T cell activation following immunization with inhibitory antigens and CpG adjuvant. Panel (E) shows T cell activation following immunization with inhibitory antigens and no adjuvant (Peptide only). Control mice were immunized with the indicated adjuvant only, or phosphate buffered saline (PBS). Peripheral blood cells of immunized mice were stimulated with overlapping peptides spanning the inhibitory antigens (Inhibitory Pool) or media only (Media), as indicated on the x-axis. Results are expressed as the number of IFNy spot forming units per 200,000 cells. Each symbol on the graphs represents the response of an individual mouse.

[0054] Figure 15 shows results of IFNy ELISpot assays for determining the immunogenicity and level of T cell activation in splenocytes of mice immunized with a pool of four inhibitory antigens in combination with the indicated adjuvant. Panel (A) shows T cell activation following immunization with inhibitory antigens and poly-IC adjuvant. Panel (B) shows T cell activation following immunization with inhibitory antigens and triple adjuvant B (Triple: CpG, 3D-PHAD, QS21). Panel (C) shows T cell activation following immunization with inhibitory antigens and incomplete Freund’s adjuvant (IFA). Panel (D) shows T cell activation following immunization with inhibitory antigens and CpG adjuvant. Panel (E) shows T cell activation following immunization with inhibitory antigens and no adjuvant (Peptide Only). Control mice were immunized with the indicated adjuvant only, or phosphate buffered saline (PBS). Splenocytes of immunized mice were stimulated with overlapping peptides spanning the inhibitory antigens (Inhibitory Pool) or media only (Media), as indicated on the x-axis. Results are expressed as the number of IFNy spot forming units per 400,000 cells. Each symbol on the graphs represents the response of an individual mouse.

[0055] Figure 16 shows results of IFNy ELISpot assays for determining the immunogenicity and level of T cell activation in lymph node cells of mice immunized with a pool of four inhibitory antigens in combination with the indicated adjuvant. Panel (A) shows T cell activation following immunization with inhibitory antigens and poly-IC adjuvant. Panel (B) shows T cell activation following immunization with inhibitory antigens and triple adjuvant B (Triple: CpG, 3D-PHAD, QS21). Panel (C) shows T cell activation following immunization with inhibitory antigens and incomplete Freund’s adjuvant. Panel (D) shows T cell activation following immunization with inhibitory antigens and CpG adjuvant. Panel (E) shows T cell activation following immunization with inhibitory antigens and no adjuvant. Control mice were immunized with the indicated adjuvant only, or phosphate buffered saline (PBS). Lymph node cells of immunized mice were stimulated with overlapping peptides spanning the inhibitory antigens (Inhibitory Pool) or media only (Media), as indicated on the x-axis. Results are expressed as the number of IFNy spot forming units per 200,000 cells. Each symbol on the graphs represents the response of an individual mouse.

[0056] Figure 17 shows the tumor volume measured in individual mice of the indicated immunization groups. Panel (A) represents the tumor volume over time (from day 0 = injection with B16F10 cancer cells) in mice immunized with triple adjuvant B only (Triple: CpG, 3D-PHAD, QS21). Panel (B) represents the tumor volume (mm³) over time (from day 0 = injection with B16F10 cancer cells) in mice immunized with a pool of four inhibitory antigens and triple adjuvant B (Triple: CpG, 3D-PHAD, QS21). Each line on the graphs represents the tumor volume (mm³) of an individual mouse.

[0057] Figure 18 shows the fold-change in tumor volume measured over time in mice immunized with a pool of 4 inhibitory antigens and the indicated adjuvant, relative to control mice immunized with adjuvant only. Immunization groups indicated on the x axis comprised poly-IC adjuvant, triple adjuvant B (Triple: CpG, 3D-PHAD, QS21), incomplete Freund’s adjuvant (IFA), CpG adjuvant, or phosphate-buffered saline (PBS). Panels (A), (B), (C), (D), and (E) represent the fold-change in tumor volume at days 7, 9, 11, 14 and 16, respectively, following injection with B16F10 cancer cells on day 0. Each bar on the graphs represents results for a group of immunized mice.

[0058] Figure 19 shows the correlation between tumor volume and IFNy spot forming units in peripheral blood cells, a measure of immunogenicity and T cell activation, for mice immunized with a pool of four inhibitory antigens in combination with triple adjuvant B (CpG, 3D-PHAD, QS21). Square symbols represent IFNy spot forming units per 200K cells. Circles represent tumor volume (mm³) on day 17 (panel A) and day 22 (panel B), following injection with B16F10 cancer cells on day 0. Each symbol on the graphs represents results for an individual mouse. Lines connect results for an individual mouse. Black indicates correlation between low IFNy (low immune response) and hyperprogressing tumor. Gray indicates correlation between higher IFNy (higher immune response) and slower progressing tumor. White indicates no correlation.

[0059] Figure 20, Panel A shows color scans of representative tumor sections from mice immunized with triple adjuvant B only (left), protective vaccine (center), or protective vaccine plus inhibigen In21 (right). Tumor sections were formalin-fixed, paraffin-embedded, stained by chromogenic immunohistochemistry (IHC) with an anti-mouse CD8a antibody, and counterstained for nuclei with hematoxylin. Endogenous melanin deposits in tumors are visible. Panel B is a graph showing mean number of infiltrating CD8⁺ T cells from multiple lOx fields per tumor isolated from mice of each vaccination group. Panel C is a graph showing flow cytometry results for CD4+ and CD8+ T cells expressing the inhibitory surface markers PD-1 and Lag3. T cells were isolated from 4 pooled tumors per vaccination group. MFI = median fluorescence intensity.

[0060] Figure 21, Panel A shows a representative flow cytometry analysis of draining lymph nodes from 4 pooled mice per vaccination group. In the left graph, CD4⁺ Foxp3⁺ cells are

+ + delineated by boxes. In the right graph, CD4 Foxp3 cells are shown as a percentage of total cells in the draining lymph node population. Panel B shows color scans of representative tumor sections from mice immunized with triple adjuvant B only (left), protective vaccine (center), or protective vaccine plus inhibigen In21 (right). Tumor sections were formalin-fixed, paraffin-embedded, stained by chromogenic immunohistochemistry (IHC) with an anti-mouse Foxp3 antibody and counterstained for nuclei with hematoxylin. Endogenous melanin deposits in tumors are visible. Panel C shows autologous dendritic and T cells from a representative human cancer patient, co-cultured and screened against previously identified stimulatory (2 wells) and inhibitory (5 wells) patient-specific antigens on the ATLAS platform. 24 hrs post co-culture, cells within the well were harvested and flow cytometry analysis of the T cells subsets performed for CD3, CD4, CD8, and Foxp3 T cell subsets. Data is representative of multiple wells containing T cells responsive to a stimulatory antigen, inhibigen, or control.

[0061] Figure 22, Panel A shows results of representative IFNy ELISpot assays using splenocytes isolated from mice vaccinated with protective vaccine or protective vaccine plus inhibigen In21. Results are expressed as the IFNy spot forming cells (SFC) per IxlO⁶ cells. Panel B shows representative viability of lymphocytes isolated from draining lymph nodes. Lymphocytes were counted in draining lymph nodes from mice of each vaccination group (n = 4 mice per group). Panel C shows representative flow cytometry analysis of splenocytes isolated from mice of each vaccination group and re-stimulated with overlapping peptides corresponding to the protective vaccine antigens M30 and Trp2 (Stim), or to M30, Trp2 and inhibigen In21 (Inhib). Gating was on + total CD3 T cells, and is presented as percent of total cells.

[0062] Figure 23 shows results of a representative killing assay, expressed as percent cytotoxicity for T cells of each vaccination group, plotted against ratio of splenocytes co-cultured with pulsed target cells (RAW309s) (denoted as E:T ratios 40:1, 20:1, 10:1). Error is the difference among replicate wells. *p = 0.028 **p=.0002.

[0063] Figure 24, Panel A shows representative PMA-stimulated ELISpot wells (left) and intracellular flow cytometry analysis of splenocytes after stimulation with anti-CD3 monoclonal antibody (right) for each vaccination group. IFNy⁺CD3⁺ T cells are delineated by boxes. Panel B corresponds to the flow cytometry analysis of Panel A, and charts the percentage of IFNy+ T cells for each vaccination group.

[0064] Figure 25 shows representative results of a sorting experiment. CD8 tumor infiltrating lymphocytes (CD8⁺, x-axis) that react with Trp2 tetramer (Trp2-tet, y-axis), and therefore express the T cell receptor for Trp2, are delineated by hexagons.

[0065] Figure 26 shows a representative time course for Experimental Autoimmune Encephalomyelitis (EAE) disease progression for groups of naive mice and mice receiving MOG35-55, MOG35-55 + MMP9FS, or MMP9FS (Study 2). Results are plotted as the EAE disease score (mean +/- SEM) for each group against study day.

[0066] Figure 27 shows representative disease-free incidence curve for groups of naive mice and mice receiving MOG35-55, MOG35-55 + MMP9FS, or MMP9FS (Study 2). Results are plotted as the percent disease-free incidence for each group against study day.

[0067] Figure 28 shows representative results of immunogenicity assays. Panel A shows IFN-gamma ELISpot results for Study 1. Panel B shows IFN-gamma ELISpot results for Study 2. IFN-gamma levels are expressed as spots per 400K splenocytes. Panel C shows flow cytometry results of Study 2 for additional cytokines IL2, IL4, IL6, IL10, IL17a, and TNF-alpha, following restimulation with the MOG35-55 peptide. Cytokine levels are expressed in pg/ml supernatant. Each symbol represents an individual mouse; horizontal lines indicate the mean +/- SEM.

[0068] Figure 29 shows myelin coverage and immune cell infiltration in myelinated (Panel A) and demyelinated (Panel B) spinal cord sections, visualized by IHC staining for the indicated markers (Study 1).

[0069] Figure 30 presents quantitative results for myelin coverage and immune cell infiltration, expressed as the percent area of myeloid IHC staining.

[0070] Figure 31 shows myelin coverage in spinal cord sections, visualized by IHC staining for MOG (black arrows; Study 2).

[0071] Figure 32 shows microglia present in spinal cord sections, visualized by IHC staining for Iba-1 (Study 2).

[0072] Figure 33 presents quantitative results for myelin coverage and immune cell infiltration, expressed as the percent area of myeloid IHC staining (in naive, MOG, M0G+MMP9 FS, and MMP FS) for plotted for % of tissue area.

[0073] Figure 34, Panels A and B show a diagram of methods, together with representative results, of an adoptive cell transfer study. Panel A shows expected tumor growth (center) and IFNy responses (bottom) in donor mice following tumor injection and vaccination with a vaccine comprising immune stimulatory antigens, a vaccine comprising the inhibitory antigen MMP9FS , or adjuvant alone. Panel B shows tumor growth in recipient mice, following tumor injection and adoptive transfer of T cells from donor mice of Panel A. Panel C shows T cell activation in recipient mice, as measured by CD4+ and CD8+ IFNy and IL-2 responses.

DEFINITIONS

[0074] Activate: As used herein, a peptide presented by an antigen presenting cell (APC) “activates” a lymphocyte if lymphocyte activity is detectably modulated after exposure to the peptide presented by the APC under conditions that permit antigen-specific recognition to occur. Any indicator of lymphocyte activity can be evaluated to determine whether a lymphocyte is activated, e.g., T cell proliferation, phosphorylation or dephosphorylation of a receptor, calcium flux, cytoskeletal rearrangement, increased or decreased expression and/or secretion of immune mediators such as cytokines or soluble mediators, increased or decreased expression of one or more cell surface markers.

[0075] Administration: As used herein, the term “administration” typically refers to the administration of a composition to a subject or system. Those of ordinary skill in the art will be aware of a variety of routes that may, in appropriate circumstances, be utilized for administration to a subject, for example a human. For example, in some embodiments, administration may be systemic or local. In some embodiments, administration may be enteral or parenteral. In some embodiments, administration may be by injection (e.g., intramuscular, intravenous, or subcutaneous injection). In some embodiments, injection may involve bolus injection, drip, perfusion, or infusion. In some embodiments administration may be topical. Those skilled in the art will be aware of appropriate administration routes for use with particular therapies described herein, for example from among those listed on www.fda.gov, which include auricular (otic), buccal, conjunctival, cutaneous, dental, endocervical, endosinusial, endotracheal, enteral, epidural, extra-amniotic, extracorporeal, interstitial, intra-abdominal, intra-amniotic, intra-arterial, intra-articular, intrabiliary, intrabronchial, intrabursal, intracardiac, intracartilaginous, intracaudal, intracavemous, intracavitary, intracerebral, intracistemal, intracorneal, intracoronal, intracorporus cavemosum, intradermal, intranodal, intradiscal, intraductal, intraduodenal, intradural, intraepidermal, intraesophageal, intragastic, intragingival, intralesional, intraluminal, intralymphatic, intramedullary, intrameningeal, intramuscular, intraocular, intraovarian, intrapericardial, intraperitoneal, intrapleural, intrapro static, intrapulmonary, intrasinal, intraspinal, intrasynovial, intratendinous, intratesticular, intrathecal, intrathoracic, intratubular, intratumor, intratympanic, intrauterine, intravascular, intravenous, intravenous bolus, intravenous drip, intraventricular, intravitreal, laryngeal, nasal, nasogastric, ophthalmic, oral, oropharyngeal, parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (e.g., inhalation), retrobulbar, soft tissue, subarachnoid, subconjunctival, subcutaneous, sublingual, submucosal, topical, transdermal, transmucosal, transplacental, transtracheal, ureteral, urethral, or vaginal. In some embodiments, administration may involve electro-osmosis, hemodialysis, infiltration, iontophoresis, irrigation, and/or occlusive dressing. In some embodiments, administration may involve dosing that is intermittent (e.g., a plurality of doses separated in time) and/or periodic (e.g., individual doses separated by a common period of time) dosing. In some embodiments, administration may involve continuous dosing.

[0076] Adoptive cell therapy. As used herein, “adoptive cell therapy” or “ACT” involves the transfer of cells (e.g., immune cells) into a subject (e.g., a subject having an autoimmune disease or overactive immune condition). In some embodiments, ACT is a treatment approach that involves the use of lymphocytes (e.g., T cells) that dampen, inhibit or suppress immune responses, the in vitro expansion of these cells to suitable numbers, and their infusion into a subject having an autoimmune disease or overactive immune condition.

[0077] Antigen: The term “antigen”, as used herein, refers to a molecule (e.g., a peptide, a polypeptide or a polysaccharide) that elicits a specific immune response. Antigen-specific immunological responses, also known as adaptive immune responses, are mediated by lymphocytes (e.g., T cells, B cells, NK cells) that express antigen receptors (e.g., T cell receptors, B cell receptors). In certain embodiments, an antigen is a T cell antigen, and elicits a cellular immune response. In certain embodiments, an antigen is a B cell antigen, and elicits a humoral (z.e., antibody) response. In certain embodiments, an antigen is both a T cell antigen and a B cell antigen. As used herein, the term “antigen” encompasses both a full-length polypeptide as well as a portion or immunogenic fragment of the polypeptide, and a peptide epitope within the polypeptides (e.g., a peptide epitope bound by a Major Histocompatibility Complex (MHC) molecule (e.g., MHC class I, or MHC class II)). In certain embodiments, an antigen is an autoantigen. In certain embodiments, an antigen is a tumor antigen. In certain embodiments, an antigen is identified from a pathogen/infectious agent. In certain embodiments, an antigen is tissue-specific or non-specific, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue.

[0078] Antigen presenting cell: An “antigen presenting cell” or “APC” refers to a cell that presents peptides on MHC class I and/or MHC class II molecules for recognition by T cells. APC include both professional APC (e.g., dendritic cells, macrophages, B cells), which have the ability to stimulate naive lymphocytes, and non-professional APC (e.g. , fibroblasts, epithelial cells, endothelial cells, glial cells). In certain embodiments, APC are able to internalize (e.g., endocytose) members of a library (e.g., cells of a library of bacterial cells) that express heterologous polypeptides as candidate antigens. [0079] Autoimmune Disease: An “autoimmune disease” as used herein refers to an immune response directed against an autoantigen.

[0080] Autolysin polypeptide'. An “autolysin polypeptide” is a polypeptide that facilitates or mediates autolysis of a cell (e.g., a bacterial cell) that has been internalized by a eukaryotic cell. In some embodiments, an autolysin polypeptide is a bacterial autolysin polypeptide. Autolysin polypeptides include, and are not limited to, polypeptides whose sequences are disclosed in GenBank® under Acc. Nos. NP 388823.1, NP 266427.1, and P0AGC3.1.

[0081] Cancer: As used herein, the term “cancer” refers to a disease, disorder, or condition in which cells exhibit relatively abnormal, uncontrolled, and/or autonomous growth, so that they display an abnormally elevated proliferation rate and/or aberrant growth phenotype characterized by a significant loss of control of cell proliferation. In some embodiments, a cancer may be characterized by one or more tumors. Those skilled in the art are aware of a variety of types of cancer including, for example, adrenocortical carcinoma, astrocytoma, basal cell carcinoma, carcinoid, cardiac, cholangiocarcinoma, chordoma, chronic myeloproliferative neoplasms, craniopharyngioma, ductal carcinoma in situ, ependymoma, intraocular melanoma, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), gestational trophoblastic disease, glioma, histiocytosis, leukemia (e.g., acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), hairy cell leukemia, myelogenous leukemia, myeloid leukemia), lymphoma (e.g., Burkitt lymphoma [non-Hodgkin lymphoma], cutaneous T cell lymphoma, Hodgkin lymphoma, mycosis fungoides, Sezary syndrome, AIDS-related lymphoma, follicular lymphoma, diffuse large B-cell lymphoma), melanoma, merkel cell carcinoma, mesothelioma, myeloma (e.g., multiple myeloma), myelodysplastic syndrome, papillomatosis, paraganglioma, pheochromacytoma, pleuropulmonary blastoma, retinoblastoma, sarcoma (e.g., Ewing sarcoma, Kaposi sarcoma, osteosarcoma, rhabdomyosarcoma, uterine sarcoma, vascular sarcoma), Wilms’ tumor, and/or cancer of the adrenal cortex, anus, appendix, bile duct, bladder, bone, brain, breast, bronchus, central nervous system, cervix, colon, endometrium, esophagus, eye, fallopian tube, gall bladder, gastrointestinal tract, germ cell, head and neck, heart, intestine, kidney (e.g., Wilms’ tumor), larynx, liver, lung (e.g., non-small cell lung cancer, small cell lung cancer), mouth, nasal cavity, oral cavity, ovary, pancreas, rectum, skin, stomach, testes, throat, thyroid, penis, pharynx, peritoneum, pituitary, prostate, rectum, salivary gland, ureter, urethra, uterus, vagina, or vulva.

[0082] Cytolysin polypeptide: A “cytolysin polypeptide” is a polypeptide that has the ability to form pores in a membrane of a eukaryotic cell. A cytolysin polypeptide, when expressed in host cell (e.g., a bacterial cell) that has been internalized by a eukaryotic cell, facilitates release of host cell components (e.g., host cell macromolecules, such as host cell polypeptides) into the cytosol of the internalizing cell. In some embodiments, a cytolysin polypeptide is bacterial cytolysin polypeptide. In some embodiments, a cytolysin polypeptide is a cytoplasmic cytolysin polypeptide. Cytolysin polypeptides include, and are not limited to, polypeptides whose sequences are disclosed in U.S. Pat. No. 6,004,815, and in GenBank® under Acc. Nos. NP 463733.1, NP 979614, NP 834769, YP 084586, YP 895748, YP 694620, YP 012823, NP 346351, YP 597752, BAB41212.2, NP 561079.1, YP 001198769, and NP 359331.1.

[0083] Cytoplasmic cytolysin polypeptide. A “cytoplasmic cytolysin polypeptide” is a cytolysin polypeptide that has the ability to form pores in a membrane of a eukaryotic cell, and that is expressed as a cytoplasmic polypeptide in a bacterial cell. A cytoplasmic cytolysin polypeptide is not significantly secreted by a bacterial cell. Cytoplasmic cytolysin polypeptides can be provided by a variety of means. In some embodiments, a cytoplasmic cytolysin polypeptide is provided as a nucleic acid encoding the cytoplasmic ccytolysin polypeptide. In some embodiments, a cytoplasmic cytolysin polypeptide is provided attached to a bead. In some embodiments, a cytoplasmic cytolysin polypeptide has a sequence that is altered relative to the sequence of a secreted cytolysin polypeptide (e.g., altered by deletion or alteration of a signal sequence to render it nonfunctional). In some embodiments, a cytoplasmic cytolysin polypeptide is cytoplasmic because it is expressed in a secretion-incompetent cell. In some embodiments, a cytoplasmic cytolysin polypeptide is cytoplasmic because it is expressed in a cell that does not recognize and mediate secretion of a signal sequence linked to the cytolysin polypeptide. In some embodiments, a cytoplasmic cytolysin polypeptide is a bacterial cytolysin polypeptide.

[0084] Heterologous'. The term “heterologous”, as used herein to refer to genes or polypeptides, refers to a gene or polypeptide that does not naturally occur in the organism in which it is present and/or being expressed, and/or that has been introduced into the organism by the hand of man. In some embodiments, a heterologous polypeptide is an antigen (e.g., an autoantigen, a tumor antigen, an antigen identified from a pathogen/infectious agent, or a tissue-specific or non-specific antigen, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue) described herein.

[0085] Immune mediator'. As used herein, the term “immune mediator” refers to any molecule that affects the cells and processes involved in immune responses. Immune mediators include cytokines, chemokines, soluble proteins, enzymes, and cell surface markers.

[0086] Improve, increase, inhibit, stimulate, suppress, or reduce : As used herein, the terms “improve”, “increase”, “inhibit”, “stimulate”, “suppress”, “reduce”, or grammatical equivalents thereof, indicate values that are relative to a baseline or other reference measurement. In some embodiments, an appropriate reference measurement may be or comprise a measurement in a particular system (e.g., in a single individual) under otherwise comparable conditions absent presence of (e.g., prior to and/or after) a particular agent or treatment, or in presence of an appropriate comparable reference agent. The effect of a particular agent or treatment may be direct or indirect. In some embodiments, an appropriate reference measurement may be or may comprise a measurement in a comparable system known or expected to respond in a particular way, in presence of the relevant agent or treatment. In some embodiments, a peptide presented by an antigen presenting cell (APC) “stimulates” or is “stimulatory” to a lymphocyte if the lymphocyte is activated to a phenotype associated with beneficial responses, after exposure to the peptide presented by the APC under conditions that permit antigen-specific recognition to occur, as observed by, e.g., T cell proliferation, phosphorylation or dephosphorylation of a receptor, calcium flux, cytoskeletal rearrangement, increased or decreased expression and/or secretion of immune mediators such as cytokines or soluble mediators, increased or decreased expression of one or more cell surface markers, relative to a control. In some embodiments, a peptide presented by an antigen presenting cell “suppresses”, “inhibits” or is “inhibitory” to a lymphocyte if the lymphocyte is activated to a phenotype associated with deleterious or non-beneficial responses, after exposure to the peptide presented by the APC under conditions that permit antigen-specific recognition to occur, as observed by, e.g., phosphorylation or dephosphorylation of a receptor, calcium flux, cytoskeletal rearrangement, increased or decreased expression and/or secretion of immune mediators such as cytokines or soluble mediators, increased or decreased expression of one or more cell surface markers, relative to a control.

[0087] Inhibitory Antigen'. An “inhibitory antigen” is an antigen that inhibits, suppresses, impairs and/or reduces immune responses (e.g., to a pathogen, or, in the context of autoimmune disease, aberrantly directed to one or more autoantigens) or immune control (e.g., of a tumor or cancer). In some embodiments, an inhibitory antigen (i) inhibits and/or suppresses level of expression and/or secretion of one or more immune mediators that increase immune response, and/or (ii) increases level of expression and/or secretion of one or more immune mediators that decrease immune response. In other embodiments, in the context of autoimmune disease or overactive immune condition, an inhibitory antigen inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject, and/or stimulates one or more lymphocyte responses that are beneficial to a subject.

[0088] Invasin polypeptide'. An “invasin polypeptide” is a polypeptide that facilitates or mediates uptake of a cell (e.g., a bacterial cell) by a eukaryotic cell. Expression of an invasin polypeptide in a noninvasive bacterial cell confers on the cell the ability to enter a eukaryotic cell. In some embodiments, an invasin polypeptide is a bacterial invasin polypeptide. In some embodiments, an invasin polypeptide is a Yersinia invasin polypeptide (e.g., a Yersinia invasin polypeptide comprising a sequence disclosed in GenBank® under Acc. No. YP 070195.1). [0089] Listeriolysin O (LLO)'. The terms “listeriolysin O” or “LLO” refer to a listeriolysin O polypeptide of Listeria monocytogenes and truncated forms thereof that retain pore-forming ability (e.g.. cytoplasmic forms of LLO, including truncated forms lacking a signal sequence). In some embodiments, an LLO is a cytoplasmic LLO. Exemplary LLO sequences are shown in Table 1, below.

[0090] Polypeptide'. The term “polypeptide”, as used herein, generally has its art-recognized meaning of a polymer of at least three amino acids. Those of ordinary skill in the art will appreciate, however, that the term “polypeptide” is intended to be sufficiently general as to encompass not only polypeptides having the complete sequence recited herein (or in a reference or database specifically mentioned herein), but also to encompass polypeptides that represent functional fragments (/.e., fragments retaining at least one activity) and immunogenic fragments of such complete polypeptides. Moreover, those of ordinary skill in the art understand that protein sequences generally tolerate some substitution without destroying activity. Thus, any polypeptide that retains activity and shares at least about 30-40% overall sequence identity, often greater than about 50%, 60%, 70%, or 80%, and further usually including at least one region of much higher identity, often greater than 90% or even 95%, 96%, 97%, 98%, or 99% in one or more highly conserved regions, usually encompassing at least 3-4 and often up to 20 or more amino acids, with another polypeptide of the same class, is encompassed within the relevant term “polypeptide” as used herein. Other regions of similarity and/or identity can be determined by those of ordinary skill in the art by analysis of the sequences of various polypeptides.

[0091] Primary cells'. As used herein, “primary cells” refers to cells from an organism that have not been immortalized in vitro. In some embodiments, primary cells are cells taken directly from a subject (e.g., a human). In some embodiments, primary cells are progeny of cells taken from a subject (e.g., cells that have been passaged in vitro). Primary cells include cells that have been stimulated to proliferate in culture.

[0092] Re-educate: As used herein, in the context of the response of a lymphocyte, “reeducate” refers to alteration in one or more responses of a lymphocyte to a particular antigen. In certain embodiments, an antigen initially stimulates one or more lymphocyte responses that are deleterious or non-beneficial to a subject, and/or the antigen initially inhibits and/or suppresses one or more lymphocyte responses that are beneficial to a subject, and such lymphocyte is re-educated such that the antigen no longer stimulates one or more lymphocyte responses that are deleterious or non- beneficial to a subject, and/or the antigen no longer inhibits and/or suppresses one or more lymphocyte responses that are beneficial to a subject. In some such embodiments, such lymphocyte is re-educated such that the antigen stimulates one or more lymphocyte responses that are beneficial to a subject and/or the antigen inhibits and/or suppresses one or more lymphocyte response that are deleterious or non-beneficial to a subject.

[0093] Redirect: As used herein, in the context of an immune response, “redirect” refers to an alteration in one or more aspects of an immune response. In certain embodiments, an initial immune response (e.g., an initial immune response to an antigen) is aberrantly directed to autoantigens, and such initial immune response is redirected such that the immune response (e.g., to the antigen) is no longer aberrantly directed to autoantigens. In some such embodiments, such redirected immune response enhances control of an autoimmune disease or overactive immune condition.

[0094] Response: As used herein, in the context of a subject (a patient or experimental organism), “response”, “responsive”, or “responsiveness” refers to an alteration in a subject’s condition that occurs as a result of, or correlates with, treatment. In certain embodiments, a response is a beneficial response.

[0095] In certain embodiments, a beneficial response can include stabilization of a subject’s condition (e.g., prevention or delay of deterioration expected or typically observed to occur absent the treatment), amelioration (e.g., reduction in frequency and/or intensity) of one or more symptoms of the condition, and/or improvement in the prospects for cure of the condition, etc. In certain embodiments, for a subject who has an autoimmune disease, a beneficial response can include: the subject has a positive clinical response to therapy or a combination of therapies for an autoimmune disease; the subject has a spontaneous reduction of an autoimmune disease; the subject is in partial or complete remission from an autoimmune disease; the subject has cleared an autoimmune disease; the subject has not had a relapse or recurrence of an autoimmune disease; cancer; the subject has a positive prognosis for an autoimmune disease; the subject has not experienced toxic responses or side effects to a therapy or combination of therapies for an autoimmune disease. In certain embodiments, for a subject who had an autoimmune disease, the beneficial responses occurred in the past, or are ongoing.

[0096] In certain embodiments, a response is a deleterious or non-beneficial response. In certain embodiments, a deleterious or non-beneficial response can include deterioration of a subject’s condition, lack of amelioration (e.g., no reduction in frequency and/or intensity) of one or more symptoms of the condition, and/or degradation in the prospects for cure of the condition, etc. In certain embodiments, for a subject who has an autoimmune disease, a deleterious or non-beneficial response can include: the subject has a negative clinical response to therapy or a combination of therapies for an autoimmune disease; the subject is not in remission from an autoimmune disease; the subject has not cleared an autoimmune condition; the subject has had a relapse or recurrence of an autoimmune disease; the subject has a negative prognosis for an autoimmune disease; the subject has experienced toxic responses or side effects to a therapy or combination of therapies for an autoimmune disease. In certain embodiments, for a subject who had an autoimmune disease, the deleterious or non-beneficial responses occurred in the past, or are ongoing.

[0097] As used herein, in the context of a cell, organ, tissue, or cell component, e.g., a lymphocyte, “response”, “responsive”, or “responsiveness” refers to an alteration in cellular activity that occurs as a result of, or correlates with, administration of or exposure to an agent, e.g. an autoantigen. In certain embodiments, a beneficial response can include increased expression and/or secretion of immune mediators associated with positive clinical responses or outcomes in a subject. In certain embodiments, a beneficial response can include decreased expression and/or secretion of immune mediators associated with negative clinical response or outcomes in a subject. In certain embodiments, a deleterious or non-beneficial response can include increased expression and/or secretion of immune mediators associated with negative clinical responses or outcomes in a subject. In certain embodiments, a deleterious or non-beneficial response can include decreased expression and/or secretion of immune mediators associated with positive clinical responses or outcomes in a subject. In certain embodiments, a response is a clinical response. In certain embodiments, a response is a cellular response. In certain embodiments, a response is a direct response. In certain embodiments, a response is an indirect response. In certain embodiments, “non-response”, “non- responsive”, or “non-responsiveness” means minimal response or no detectable response. In certain embodiments, a “minimal response” includes no detectable response. In certain embodiments, presence, extent, and/or nature of response can be measured and/or characterized according to particular criteria. In certain embodiments, such criteria can include clinical criteria and/or objective criteria. In certain embodiments, techniques for assessing response can include, but are not limited to, clinical examination, positron emission tomography, chest X-ray, CT scan, MRI, ultrasound, endoscopy, laparoscopy, presence or level of a particular marker in a sample, cytology, and/or histology. The exact response criteria can be selected in any appropriate manner, provided that when comparing groups of patients or experimental organism, and/or cells, organs, tissues, or cell components, the groups to be compared are assessed based on the same or comparable criteria for determining response rate. One of ordinary skill in the art will be able to select appropriate criteria.

[0098] Stimulatory Antigen'. A “stimulatory antigen” is an antigen that increases and/or stimulates immune responses (e.g., to a pathogen, or, in the context of autoimmune disease, aberrantly directed to one or more autoantigens) or immune control (e.g., of a tumor or cancer). In some embodiments, a stimulatory antigen (i) inhibits and/or suppresses level of expression and/or secretion of one or more immune mediators that decrease immune response, and/or (ii) increases level of expression and/or secretion of one or more immune mediators that increase immune response. In other embodiments, in the context of autoimmune disease, a stimulatory antigen stimulates one or more lymphocyte responses that are deleterious or non-beneficial to a subject, and/or inhibits and/or suppresses one or more lymphocyte responses that are beneficial to a subject.

[0099] Tumor. As used herein, the term “tumor” refers to an abnormal growth of cells or tissue. In some embodiments, a tumor may comprise cells that are precancerous (e.g., benign), malignant, pre-metastatic, metastatic, and/or non-metastatic. In some embodiments, a tumor is associated with, or is a manifestation of, a cancer. In some embodiments, a tumor may be a disperse tumor or a liquid tumor. In some embodiments, a tumor may be a solid tumor.

DETAILED DESCRIPTION

[0100] The present disclosure provides methods and systems for the rapid identification of antigens (e.g., autoantigens, tumor antigens, antigens identified from pathogens/infectious agents; and tissue-specific or non-specific antigens, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue) that elicit T cell responses and particularly that elicit human T cell responses. For purposes of this disclosure, “antigens” includes both antigens and potential antigens. Antigens of the present disclosure include “inhibitory” antigens that are characterized e.g., in their ability to dampen (i.e., decrease) an immune (e.g., an autoimmune) response in a subject.

[0101] The present disclosure provides, among other things, a method of treating a subject that suffers from or is susceptible to an autoimmune disease or overactive immune condition by administering to a subject an immunogenic composition that includes at least one inhibitory antigen identified to (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response. The at least one inhibitory antigen of the immunogenic composition may be related or unrelated to the autoimmune disease or overactive immune condition of the subject, e.g., the inhibitory antigen may be identified from a tumor or cancer cell, or from an infectious agent/pathogen.

[0102] As described herein, methods of the present disclosure identified stimulatory antigens (e.g., tumor antigens) that were not identified by known algorithms. Further, methods of the present disclosure identified suppressive and/or inhibitory antigens that are not identifiable by known algorithms. Methods of the present disclosure also identified polypeptides that are potential antigens, i.e., polypeptides that activate T cells of non-cancerous subjects, but not T cells of subjects suffering from cancer. The present disclosure also provides methods of selecting inhibitory antigens, methods of using the selected inhibitory antigens (e.g., to treat a subject suffering from or susceptible to an autoimmune disease or overactive immune condition), immunogenic compositions comprising the selected inhibitory antigens, and methods of manufacturing immunogenic compositions. Autoimmune Disease and Therapies

[0103] The present disclosure provides methods for identifying antigens (e.g., inhibitory antigens) and administering an immunogenic composition comprising one or more identified antigens to a subject suffering from or susceptible to an autoimmune disease or overactive immune condition.

[0104] ATLAS (Genocea Biosciences) is the only existing platform for rapid, high- throughput quantification of pre-existing, antigen-specific CD4⁺ and CD8⁺ T cell responses without the use of algorithms or in silico downselection criteria, and has previously yielded antigens with clinical efficacy when administered as a vaccine (Bernstein, D. I. et al. Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial. J Infect Dis 215, 856- 864, doi:10.1093/infdis/jix004 (2017)). Patient antigen presenting cells, e.g., MDDC, are pulsed with an ordered array of Escherichia coli expressing patient-specific mutations as short polypeptides, with or without co-expressed listeriolysin O (cLLO) facilitating HLA class I or class II presentation, respectively. CD8⁺ or CD4⁺ T cells are subsequently added, and after an overnight incubation, antigens are differentially characterized as stimulatory or inhibitory by significant up- or downregulation of T cell cytokine secretion relative to control responses; thus, the ATLAS assay allows for identification and characterization of antigens that dampen autoimmune or overactive immune responses.

[0105] Methods of the present disclosure are useful for treating or ameliorating an autoimmune disease or overactive immune condition (e.g., Type I diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and/or a vasculitis). In some embodiments, methods include identifying antigens associated with a decreased immune response (e.g., an inhibitory antigen) and administering a composition comprising one or more of the identified antigens to dampen immune response in a subject suffering from an autoimmune disease or overactive immune condition. In some embodiments, the identified antigens are used to generate a population of inhibitory antigen-specific T cells ex vivo, which is then administered to a subject as an adoptive cell therapy, where the subject suffers from an autoimmune disease or overactive immune condition.

[0106] In some embodiments, a method of attenuating or decreasing and immune response in a subject with an autoimmune disease is provided, comprising: administering to the subject a vaccine, comprising an inhibigen and an effective amount of an adjuvant. In some embodiments, the inhibigen is a peptide. In some embodiments, the peptide is encoded by a nucleic acid. In some embodiments, the nucleic acid is a vector. In some embodiments, the nucleic acid is an RNA, optionally wherein the RNA is an mRNA. In some embodiments, the inhibigen is obtained by a method comprising a) providing a plurality of bacterial cells or beads, wherein each bacterial cell or bead comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with human antigen presenting cells (APCs); c) contacting the APCs with a plurality of human lymphocytes; e) identifying one or more polypeptides that inhibit and/or suppress cytolytic T cell activity; and I) selecting one or more inhibitory polypeptides; thereby selecting the inhibigen. In some embodiments, the administration of the vaccine results in a decreased IFNy cytokine production by the immune cells of the subject. In some embodiments, the vaccine reduces or abolishes cytolytic T cell activity. In some embodiments, the autoimmune disease is multiple sclerosis.

Types of Autoimmune Disease

[0107] In some embodiments, an autoimmune disease can be any known autoimmune disease or condition associated with an autoimmune disease. In some embodiments, an autoimmune disease is one of achalasia, Addison’s disease, adult Still's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM/anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune dysautonomia, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, axonal & neuronal neuropathy (AMAN), Balo disease, asthma, Behcet’s disease, aenign mucosal pemphigoid, aullous pemphigoid, Castleman disease (CD), celiac disease, Chagas disease, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss Syndrome (CSS) or eosinophilic granulomatosis (EGPA), cicatricial pemphigoid, Cogan’s syndrome, cold agglutinin disease, congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn’s disease, dermatitis herpetiformis, dermatomyositis, Devic’s disease (neuromyelitis optica), discoid lupus, Dressier’s syndrome, endometriosis, eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture’s syndrome, granulomatosis with polyangiitis, Graves’ disease, Guillain-Barre syndrome, transplant rejection/graft versus host disease (GVHD), Hashimoto’s thyroiditis, hemolytic anemia, Henoch-Schonlein purpura (HSP), Herpes gestationis or pemphigoid gestationis (PG), hidradenitis S\suppurativa (HS) (acne inversa), hypogammalglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, immune thrombocytopenic purpura (ITP), inclusion body myositis (IBM), interstitial cystitis (IC), juvenile arthritis juvenile diabetes (Type 1 diabetes), juvenile myositis (JM), Kawasaki disease, Lambert- Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease (LAD), lupus, lyme disease chronic, Meniere’s disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, multifocal motor neuropathy (MMN) or MMNCB, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, Nneonatal lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism (PR), PANDAS, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Pars planitis (peripheral uveitis), Parsonage-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndromes type I, II, III, polymyalgia rheumatica, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia (PRCA), pyoderma gangrenosum, Raynaud’s phenomenon, reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren’s syndrome, sperm & testicular autoimmunity, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac’s syndrome, sympathetic ophthalmia (SO), Takayasu’s arteritis, temporal arteritis/giant cell arteritis, thrombocytopenic purpura (TTP), thyroid eye disease (TED), Tolosa-Hunt syndrome (THS), transverse myelitis, Type 1 diabetes, ulcerative colitis (UC), undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vitiligo, or Vogt-Koyanagi-Harada disease (autoimmune disease list according to the AARDA https://www.aarda.org/diseaselist/ ).

[0108] In some embodiments, an autoimmune disease is an inflammatory autoimmune condition. Examples of inflammatory autoimmune conditions include autoimmune (Hashimoto's) thyroiditis, hyperthyroidism (Grave's disease), autoimmune adrenal insufficiency (Addison's disease), autoimmune oophoritis, autoimmune orchitis, autoimmune hepatitis, autoimmune hemolytic anemia, paroxysmal cold hemoglobinuria, autoimmune thrombocytopenia, autoimmune neutropenia, pernicius anemia, pure red cell anemia, autoimmune coagulopathies, myasthenia gravis, autoimmune polyneuritis, multiple sclerosis, pemphigus and other bullous diseases, rheumatic carditis, Goodpasture's syndrome, postcardiotomy syndrome, systemic lupus erythematosus, Sjorgen's syndrome, polymyositis, dermatomyositis, scleroderma, inflammatory bowel diseases: Crohn's disease, ulcerative colitis; chronic obstructive pulmonary diseases, chronic inflammatory diseases, celiac disease, vasculitis, Wegener's disease, Churg-Strauss syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, cardiovascular disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis juvenile idiopathic arthritis, poly dermatomyositis, septic shock, host versus graft disease, graft versus host disease, asthma, rhinitis, psoriasis, cachexia associated with cancer, eczema, vitiligo, Reiter's syndrome, Kawasaki's disease, idiopathic thrombocytopenic purpura, Guillain-Barre syndrome, antiphospholipid antibody syndrome (APS), atherosclerosis, and narcolepsy.

[0109] In some embodiments, an autoimmune disease is systemic lupus erythematosus (SLE). SLE is associated with excessive complement activation, which can cause tissue damage. SLE can affect the joints, skin, kidneys, blood cells, brain, heart, and lungs. SLE symptoms vary but can include fatigue, joint pain, rash, and fever, which can periodically get worse (flare-up). [0110] In some embodiments, an autoimmune disease is Henoch Schonlein purpura (HSP) nephritis.

[oni] In some embodiments, an autoimmune disease is antiphospholipid antibody syndrome (APS). APS is a clinical entity that encompasses thrombosis, recurrent miscarriages, and pregnancy -related complications, mediated by anti-phospholipid antibodies (APLA). One of the important mechanisms in the initiation and formation of thrombus in APS is by complement activation. Levels of C3a and C4a are also higher in patients with primary APS.

[0112] In some embodiments, an autoimmune disease is a vasculitis. Vasculitis is an inflammation of the blood vessels. It happens when the body's immune system attacks the blood vessel by mistake. It can happen because of an infection, a medicine, or another disease. There are many types of vasculitis. They are classified according to the size of the blood vessels affected. Vasculitis affecting large vessels include: Polymyalgia rheumatic, Takayasu's arteritis, temporal arteritis (and giant cell arteritis). Vasculitis affecting medium vessels include: Buerger's disease, cutaneous vasculitis, Kawasaki disease, polyarteritis nodosa. Vasculitis affecting small vessels include: Behcet's syndrome, Churg-Strauss syndrome, cutaneous vasculitis, Henoch-Schbnlein purpura, microscopic polyangiitis, Granulomatosis with polyangiitis (GPA), Golfer's vasculitis, and cryoglobulinemia.

[0113] In some embodiments, an autoimmune disease is rheumatoid arthritis (RA). Serum concentrations of C3 and C4 may be elevated in RA. Similarly, levels of complement cleavage products such as C3a, C5a, C5b-9 are elevated in the synovial fluid of RA subjects.

Library generation

[0114] A library is a collection of members (e.g., cells or non-cellular particles, such as virus particles, liposomes, or beads (e.g., beads coated with polypeptides, such as in vitro translated polypeptides, e.g., affinity beads, e.g., antibody coated beads, or NTA-Ni beads bound to polypeptides of interest). According to the present disclosure, members of a library include (e.g., internally express or carry) polypeptides of interest described herein. In some embodiments, members of a library are cells that internally express polypeptides of interest described herein. In some embodiments, polypeptides of interest are polypeptides derived from a pathogen/infectious agent, or from a target cell of interest (e.g., a tumor cell, a cell that is a target of an autoimmune response, or a healthy cell). In some embodiments, members of a library which are particles carry, and/or are bound to, polypeptides of interest. Use of a library in an assay system allows simultaneous evaluation in vitro of cellular responses to multiple candidate antigens. According to the present disclosure, a library is designed to be internalized by human antigen presenting cells so that peptides from library members, including peptides from internally expressed polypeptides of interest, are presented on MHC molecules of the antigen presenting cells for recognition by T cells. [0115] Libraries can be used in assays that detect peptides presented by human MHC class I and MHC class II molecules. Polypeptides expressed by the internalized library members are digested in intracellular endocytic compartments (e.g., phagosomes, endosomes, lysosomes) of the human cells and presented on MHC class II molecules, which are recognized by human CD4⁺ T cells. In some embodiments, library members include a cytolysin polypeptide, in addition to a polypeptide of interest. In some embodiments, library members include an invasin polypeptide, in addition to the polypeptide of interest. In some embodiments, library members include an autolysin polypeptide, in addition to the polypeptide of interest. In some embodiments, library members are provided with cells that express a cytolysin polypeptide (i.e., the cytolysin and polypeptide of interest are not expressed in the same cell, and an antigen presenting cell is exposed to members that include the cytolysin and members that include the polypeptide of interest, such that the antigen presenting cell internalizes both, and such that the cytolysin facilitates delivery of polypeptides of interest to the MHC class I pathway of the antigen presenting cell). A cytolysin polypeptide can be constitutively expressed in a cell, or it can be under the control of an inducible expression system (e.g., an inducible promoter). In some embodiments, a cytolysin is expressed under the control of an inducible promoter to minimize cytotoxicity to the cell that expresses the cytolysin.

[0116] Once internalized by a human cell, a cytolysin polypeptide perforates intracellular compartments in the human cell, allowing polypeptides expressed by the library members to gain access to the cytosol of the human cell. Polypeptides released into the cytosol are presented on MHC class I molecules, which are recognized by CD8⁺ T cells.

[0117] A library can include any type of cell or particle that can be internalized by and deliver a polypeptide or DNA encoding a polypeptide of interest (and a cytolysin polypeptide, in applications where a cytolysin polypeptide is desirable) to, antigen presenting cells for use in methods described herein. Although the term “cell” is used throughout the present specification to refer to a library member, it is understood that, in some embodiments, the library member is a non-cellular particle, such as a virus particle, liposome, or bead. In some embodiments, members of the library include polynucleotides that encode the polypeptide of interest (and cytolysin polypeptide), and can be induced to express the polypeptide of interest (and cytolysin polypeptide) prior to, and/or during internalization by antigen presenting cells.

[0118] In some embodiments, the cytolysin polypeptide is heterologous to the library cell in which it is expressed, and facilitates delivery of polypeptides expressed by the library cell into the cytosol of a human cell that has internalized the library cell. Cytolysin polypeptides include bacterial cytolysin polypeptides, such as listeriolysin O (LLO), streptolysin O (SLO), and perfringolysin O (PFO). Additional cytolysin polypeptides are described in U.S. Pat. 6,004,815. In certain embodiments, library members express LLO. In some embodiments, a cytolysin polypeptide is not significantly secreted by the library cell (e.g., less than 20%, 10%, 5%, or 1% of the cytolysin polypeptide produced by the cell is secreted). For example, the cytolysin polypeptide is a cytoplasmic cytolysin polypeptide, such as a cytoplasmic LLO polypeptide (e.g., a form of LLO which lacks the N-terminal signal sequence, as described in Higgins et al., Mol. Microbiol. 31(6): 1631-1641, 1999). Exemplary cytolysin polypeptide sequences are shown in Table 1. The listeriolysin O (A3-25) sequence shown in the second row of Table 1 has a deletion of residues 3-25, relative to the LLO sequence in shown in the first row of Table 1, and is a cytoplasmic LLO polypeptide. In some embodiments, a cytolysin is expressed constitutively in a library host cell. In other embodiments, a cytolysin is expressed under the control of an inducible promoter. Cytolysin polypeptides can be expressed from the same vector, or from a different vector, as the polypeptide of interest in a library cell.

Table 1. Exemplary Cytolysin Polypeptides

[0119] In some embodiments, a library member (e.g., a library member which is a bacterial cell) includes an invasin that facilitates uptake by the antigen presenting cell. In some embodiments, a library member includes an autolysin that facilitates autolysis of the library member within the antigen presenting cell. In some embodiments, a library member includes both an invasin and an autolysin. In some embodiments, a library member which is an E. coli cell includes an invasin and/or an autolysin. In various embodiments, library cells that express an invasin and/or autolysin are used in methods that also employ non-professional antigen presenting cells or antigen presenting cells that are from cell lines. Isberg et al. (Cell, 1987, 50:769-778), Sizemore et al. (Science, 1995, 270:299- 302) and Courvalin et al. (C.R. Acad. Sci. Paris, 1995, 318:1207-12) describe expression of an invasin to effect endocytosis of bacteria by target cells. Autolysins are described by Cao et al., Infect. Immun. 1998, 66(6): 2984-2986; Margot et al. , J. Bacterial. 1998, 180(3):749-752; Buist et al., Appl. Environ. Microbiol., 1997, 63(7) :2722 -2728; Yamanaka et al., FEMS Microbiol. Lett., 1997, 150(2): 269-275; Romero et al., FEMS Microbiol. Lett., 1993, 108(l):87-92; Betzner and Keck, Mol. Gen. Genet., 1989, 219(3): 489-491; Lubitz et al., J. Bacterial., 1984, 159(l):385-387; and Tomasz et al., J. Bacterial., 1988, 170(12): 5931-5934. In some embodiments, an autolysin has a feature that permits delayed lysis, e.g., the autolysin is temperature -sensitive or time-sensitive (see, e.g, Chang et al., 1995, J. Bact. 177, 3283-3294; Raab et al., 1985, J. Mol. Biol. 19, 95-105; Gerds et al., 1995, Mol. Microbiol. 17, 205-210). Useful cytolysins also include addiction (poison/antidote) autolysins, (see, e.g., Magnuson R, et al., 1996, J. Biol. Chem. 271(31), 18705-18710; Smith A S, et al., 1997, Mol. Microbiol. 26(5), 961-970).

[0120] In some embodiments, members of the library include bacterial cells. In certain embodiments, the library includes non-pathogenic, non-virulent bacterial cells. Examples of bacteria for use as library members include E. coli, mycobacteria, Listeria monocytogenes, Shigella flexneri, Bacillus subtilis, or Salmonella.

[0121] In some embodiments, members of the library include eukaryotic cells (e.g., yeast cells). In some embodiments, members of the library include viruses (e.g., bacteriophages). In some embodiments, members of the library include liposomes. Methods for preparing liposomes that include a cytolysin and other agents are described in Kyung-Dall et al., U.S. Pat. No. 5,643,599. In some embodiments, members of the library include beads. Methods for preparing libraries comprised of beads are described, e.g., in Lam et al., Nature 354: 82-84, 1991, U.S. Pat. Nos. 5,510,240 and 7,262,269, and references cited therein.

[0122] In certain embodiments, a library is constructed by cloning polynucleotides encoding polypeptides of interest, or portions thereof, into vectors that express the polypeptides of interest in cells of the library. The polynucleotides can be synthetically synthesized. The polynucleotides can be cloned by designing primers that amplify the polynucleotides. Primers can be designed using available software, such as Primer3Plus (available the following URL: bioinformatics.nl/cgi- bin/primer3plus/primer3plus.cgi; see Rozen and Skaletsky, In: Krawetz S, Misener S (eds) Bioinformatics Methods and Protocols: Methods in Molecular Biology. Humana Press, Totowa, NJ, pp. 365-386, 2000). Other methods for designing primers are known to those of skill in the art. In some embodiments, primers are constructed so as to produce polypeptides that are truncated, and/or lack hydrophobic regions (e.g., signal sequences or transmembrane regions) to promote efficient expression. The location of predicted signal sequences and predicted signal sequence cleavage sites in a given open reading frame (ORF) sequence can be determined using available software, see, e.g, Dvrlov et al., J. Mol. Biol., 340:783-795, 2004, and the following URL: cbs.dtu.dk/services/SignalP/). For example, if a signal sequence is predicted to occur at the N-terminal 20 amino acids of a given polypeptide sequence, a primer is designed to anneal to a coding sequence downstream of the nucleotides encoding the N-terminal 20 amino acids, such that the amplified sequence encodes a product lacking this signal sequence.

[0123] Primers can also be designed to include sequences that facilitate subsequent cloning steps. ORFs can be amplified directly from genomic DNA (e.g., genomic DNA of a tumor cell), or from polynucleotides produced by reverse transcription (RT-PCR) of mRNAs expressed by the tumor cell. RT-PCR of mRNA is useful, e.g, when the genomic sequence of interest contains intronic regions. PCR-amplified ORFs are cloned into an appropriate vector, and size, sequence, and expression of ORFs can be verified prior to use in immunological assays.

[0124] In some embodiments, a polynucleotide encoding a polypeptide of interest is linked to a sequence encoding a tag (e.g., an N-terminal or C-terminal epitope tag) or a reporter protein (e.g., a fluorescent protein). Epitope tags and reporter proteins facilitate purification of expressed polypeptides, and can allow one to verily that a given polypeptide is properly expressed in a library host cell, e.g., prior to using the cell in a screen. Useful epitope tags include, for example, a polyhistidine (His) tag, a V5 epitope tag from the P and V protein of paramyxovirus, a hemagglutinin (HA) tag, a myc tag, and others. In some embodiments, a polynucleotide encoding a polypeptide of interest is fused to a sequence encoding a tag which is a known antigenic epitope (e.g., an MHC class I- and/or MHC class Il-restricted T cell epitope of a model antigen such as an ovalbumin), and which can be used to verify that a polypeptide of interest is expressed and that the polypeptide -tag fusion protein is processed and presented in antigen presentation assays. In some embodiments a tag includes a T cell epitope of a murine T cell (e.g., a murine T cell line). In some embodiments, a polynucleotide encoding a polypeptide of interest is linked to a tag that facilitates purification and a tag that is a known antigenic epitope. Useful reporter proteins include naturally occurring fluorescent proteins and their derivatives, for example, Red Fluorescent Protein (FresnoRFP), Green Fluorescent Protein (Aequorea Victoria) and Neon Green (Branchiostoma lanceolatum). Panels of synthetically derived fluorescent and chromogenic proteins are also available from commercial sources.

[0125] Polynucleotides encoding a polypeptide of interest are cloned into an expression vector for introduction into library host cells. Various vector systems are available to facilitate cloning and manipulation of polynucleotides, such as the Gateway® Cloning system (Invitrogen). As is known to those of skill in the art, expression vectors include elements that drive production of polypeptides of interest encoded by a polynucleotide in library host cells (e.g., promoter and other regulatory elements). In some embodiments, polypeptide expression is controlled by an inducible element (e.g., an inducible promoter, e.g., an IPTG- or arabinose- inducible promoter, or an IPTG- inducible phage T7 RNA polymerase system, a lactose (lac) promoter, a tryptophan (trp) promoter, a tac promoter, a trc promoter, a phage lambda promoter, an alkaline phosphatase (phoA) promoter, to give just a few examples; see Cantrell, Meth, in Mol. Biol., 235:257-276, Humana Press, Casali and Preston, Eds.). In some embodiments, polypeptides are expressed as cytoplasmic polypeptides. In some embodiments, the vector used for polypeptide expression is a vector that has a high copy number in a library host cell. In some embodiments, the vector used for expression has a copy number that is more than 25, 50, 75, 100, 150, 200, or 250 copies per cell. In some embodiments, the vector used for expression has a ColEl origin of replication. Useful vectors for polypeptide expression in bacteria include pGEN vectors (Genscript), pET vectors (Novagen), Gateway® pDEST vectors (Invitrogen), pGEX vectors (Amersham Biosciences), pPRO vectors (BD Biosciences), pBAD vectors (Invitrogen), pLEX vectors (Invitrogen), pMAL™ vectors (New England BioLabs), pGEMEX vectors (Promega), and pQE vectors (Qiagen). Vector systems for producing phage libraries are known and include Novagen T7Select® vectors, and New England Biolabs Ph.D.™ Peptide Display Cloning System.

[0126] In some embodiments, library host cells express (either constitutively, or when induced, depending on the selected expression system) a polypeptide of interest to at least 10%, 20%, 30%, 40%, 50%, 60%, or 70% of the total cellular protein. In some embodiments, the level of a polypeptide available in or on a library member (e.g., cell, virus particle, liposome, bead) is such that antigen presenting cells exposed to a sufficient quantity of the library members are presented on MHC molecules polypeptide epitopes at a density that is comparable to the density presented by antigen presenting cells pulsed with purified peptides.

[0127] Methods for efficient, large-scale production of libraries are available. For example, site-specific recombinases or rare-cutting restriction enzymes can be used to transfer polynucleotides between expression vectors in the proper orientation and reading frame (Walhout et al., Meth. Enzymol. 328:575-592, 2000; Marsischky et al., Genome Res. 14:2020-202, 2004; Blommel et al., Protein Expr. Purif. 47:562-570, 2006).

[0128] For production of liposome libraries, expressed polypeptides (e.g., purified or partially purified polypeptides) can be entrapped in liposomal membranes, e.g., as described in Wassef et al., U.S. Pat. No. 4,863,874; Wheatley et al., U.S. Pat. No. 4,921,757; Huang et al., U.S. Pat. No. 4,925,661; or Martin et al., U.S. Pat. No. 5,225,212.

[0129] A library can be designed to include full length polypeptides and/or portions of polypeptides. Expression of full-length polypeptides maximizes epitopes available for presentation by a human antigen presenting cell, thereby increasing the likelihood of identifying an antigen. However, in some embodiments, it is useful to express portions of polypeptides, or polypeptides that are otherwise altered, to achieve efficient expression. For example, in some embodiments, polynucleotides encoding polypeptides that are large (e.g., greater than 1,000 amino acids), that have extended hydrophobic regions, signal peptides, transmembrane domains, or domains that cause cellular toxicity, are modified (e.g., by C-terminal truncation, N-terminal truncation, or internal deletion) to reduce cytotoxicity and permit efficient expression a library cell, which in turn facilitates presentation of the encoded polypeptides on human cells. Other types of modifications, such as point mutations or codon optimization, may also be used to enhance expression.

[0130] The number of polypeptides included in a library can be varied. For example, in some embodiments, a library can be designed to express polypeptides from at least 5%, 10%, 15%, 20%, 25%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more, of ORFs in a target cell (e.g., tumor cell). In some embodiments, a library expresses at least 10, 15, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 2500, 5000, 10,000, or more different polypeptides of interest, each of which may represent a polypeptide encoded by a single full length polynucleotide or portion thereof.

[0131] In some embodiments, assays may focus on identifying antigens that are secreted polypeptides, cell surface -expressed polypeptides, or virulence determinants, e.g., to identify antigens that are likely to be targets of both humoral and cell mediated immune responses.

[0132] In some embodiments, assays focus on identifying antigens to any pathogen or agent that infects humans. For example, libraries can be designed to express polypeptides encoded by viruses, bacteria, fungi, protozoa, or helminths that infect humans.

[0133] In some embodiments, members of a library include polynucleotides that encode polypeptides from a virus. For example, a library can be designed to express polypeptides from one of the following viruses: an immunodeficiency virus (e.g., a human immunodeficiency virus (HIV), e.g, HIV-1, HIV-2), a hepatitis virus (e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis A virus, non-A and non-B hepatitis virus), a herpes virus (e.g., herpes simplex virus type I (HSV-1), HSV-2, Varicella-zoster virus, Epstein Barr virus, human cytomegalovirus, human herpesvirus 6 (HHV-6), HHV-7, HHV-8), a poxvirus (e.g., variola, vaccinia, monkeypox, Molhiscum contagiosum virus), an influenza virus, a human papilloma virus, adenovirus, rhinovirus, coronavirus, respiratory syncytial virus, rabies virus, coxsackie virus, human T-cell leukemia virus (types I, II and III), parainfluenza virus, paramyxovirus, poliovirus, rotavirus, rhinovirus, rubella virus, measles virus, mumps virus, adenovirus, yellow fever virus, Norwalk virus, West Nile virus, a Dengue virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), bunyavirus, Ebola virus, Marburg virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Japanese encephalitis virus, St. Louis encephalitis virus, Junin virus, Lassa virus, and Lymphocytic choriomeningitis virus. Libraries for other viruses can also be produced and used according to methods described herein.

[0134] In some embodiments, members of a library include polynucleotides that encode polypeptides from bacteria (e.g., from a bacterial pathogen). In some embodiments, the bacterial pathogen is an intracellular pathogen. In some embodiments, the bacterial pathogen is an extracellular pathogen. Examples of bacterial pathogens include bacteria from the following genera and species: Chlamydia (e.g., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis), Legionella (e.g., Legionella pneumophila), Listeria (e.g., Listeria monocytogenes), Rickettsia (e.g., R. australis, R. rickettsii, R. akari, R. conorii, R. sibirica, R. japonica, R. africae, R. typhi, R. prowazekii), Actinobacter (e.g., Actinobacter baumannii), Bordetella (e.g., Bordetella pertussis), Bacillus (e.g., Bacillus anthracis, Bacillus cereus), Bacteroides (e.g., Bacteroides fragilis), Bartonella (e.g., Bartonella henselae), Borrelia (e.g., Borrelia burgdorferi), Brucella (e.g., Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis), Campylobacter (e.g., Campylobacter jejuni), Clostridium (e.g., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani), Corynebacterium (e.g., Corynebacterium diphtheriae, Corynebacterium amycolatum), Enterococcus (e.g., Enterococcus faecalis, Enterococcus faecium), Escherichia (e.g., Escherichia coli), Francisella (e.g., Francisella tularensis), Haemophilus (e.g., Haemophilus influenzae), Helicobacter (e.g., Helicobacter pylori), Klebsiella (e.g., Klebsiella pneumoniae), Leptospira (e.g., Leptospira interrogans), Mycobacteria (e.g., Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma (e.g., Mycoplasma pneumoniae), Neisseria (e.g., Neisseria gonorrhoeae, Neisseria meningitidis), Pseudomonas (e.g., Pseudomonas aeruginosa), Salmonella (e.g., Salmonella typhi, Salmonella typhimurium, Salmonella enterica), Shigella (e.g., Shigella dysenteriae, Shigella sonnei), Staphylococcus (e.g., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus), Streptococcus (e.g., Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes), Treponoma (e.g., Treponoma pallidum), Vibrio (e.g., Vibrio cholerae, Vibrio vulnificus), and Yersinia (e.g., Yersinia pestis). Libraries for other bacteria can also be produced and used according to methods described herein.

[0135] In some embodiments, members of a library include polynucleotides that encode polypeptides from protozoa. Examples of protozoal pathogens include the following organisms: Cryptosporidium parvum, Entamoeba (e.g., Entamoeba histolytica), Giardia (e.g., Giardia lambda), Leishmania (e.g., Leishmania donovani), Plasmodium spp. (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae), Toxoplasma (e.g., Toxoplasma gondii), Trichomonas (e.g., Trichomonas vaginalis), and Trypanosoma (e.g., Trypanosoma brucei, Trypanosoma cruzi). Libraries for other protozoa can also be produced and used according to methods described herein.

[0136] In some embodiments, members of a library include polynucleotides that encode polypeptides from a fungus. Examples of fungal pathogens include the following: Aspergillus, Candida (e.g., Candida albicans), Coccidiodes (e.g., Coccidiodes immitis), Cryptococcus (e.g., Cryptococcus neoformans), Histoplasma (e.g., Histoplasma capsulatum), and Pneumocystis (e.g., Pneumocystis carinii). Libraries for other fungi can also be produced and used according to methods described herein.

[0137] In some embodiments, members of a library include polynucleotides that encode polypeptides from a helminth Examples of helminthic pathogens include Ascaris lumbricoides, Ancylostoma, Clonorchis sinensis, Dracuncula medinensis, Enterobius vermicularis, Filaria, Onchocerca volvulus, Loa loa, Schistosoma, Strongyloides, Trichuris trichura, and Trichinella spiralis. Libraries for other helminths can also be produced and used according to methods described herein.

[0138] Sequence information for genomes and ORFs for infectious agents is publicly available. See, e.g, the Entrez Genome Database (URL: ncbi.nlm.nih.gov/sites/entrez?db =Genome&itool=toolbar) and the ERGO™ Database (URL: igweb.integratedgenomics. com/ERGO_supplement/genomes.html), the Genomes Online Database (GOLD) (URL: genomesonline.org) (Liolios et al., Nucleic Acids Res. 1; 34(Database issue):D332-4, 2006).

[0139] In some embodiments, members of a library include polynucleotides that encode polypeptides from a target cell of interest. In some embodiments, a target cell of interest is a tumor cell. In some embodiments, a target cell of interest is a cell identified as a target of autoimmune response.

[0140] In some embodiments, members of a library include polynucleotides that encode polypeptides that are derived from a healthy tissue of a subject.

[0141] In addition to polypeptides of interest, libraries can include tags or reporter proteins that allow one to easily purify, analyze, or evaluate MHC presentation, of the polypeptide of interest. In some embodiments, polypeptides expressed by a library include C-terminal tags that include both an MHC class I and an MHC class Il-restricted T cell epitope from a model antigen, such as chicken ovalbumin (OVA). Library protein expression and MHC presentation is validated using these epitopes. In some embodiments, the epitopes are OVA247-265 and OVA258-265 respectfully, corresponding to positions in the amino acid sequence found in GenBank® under Acc. No.

NP 990483. Expression and presentation of linked ORFs can be verified with antigen presentation assays using T cell hybridomas (e.g., B3Z T hybridoma cells, which are H2-K^b restricted, and KZO T hybridoma cells, which are H2-A^k restricted) that specifically recognize these epitopes.

[0142] Sets of library members (e.g., bacterial cells) can be provided on an array (e.g., on a solid support, such as a 96-well plate) and separated such that members in each location express a different polypeptide of interest, or a different set of polypeptides of interest.

[0143] Methods of using library members for identifying T cell antigens are described in detail below. In addition to these methods, library members also have utility in assays to identify B cell antigens. For example, lysate prepared from library members that include polypeptides of interest can be used to screen a sample comprising antibodies (e.g., a serum sample) from a subject (e.g., a subject who has been exposed to an infectious agent of interest, a subject who has cancer, and/or a control subject), to determine whether antibodies present in the subject react with the polypeptide of interest. Suitable methods for evaluating antibody reactivity are known and include, e.g., ELISA assays.

Polypeptides of Interest

[0144] In some embodiments, methods and compositions described herein can be used to identify and/or detect immune responses to a polypeptide of interest. In some embodiments, a polypeptide of interest is encoded by an ORF from a target cell (e.g., a tumor cell, or a cell that is the target of an autoimmune response), and members of a library include (e.g., internally express or carry) ORFs from a target cell. In some such embodiments, a library can be used in methods described herein to assess immune responses to one or more polypeptides of interest encoded by one or more ORFs. In some embodiments, methods of the disclosure identify one or more polypeptides of interest as stimulatory antigens (e.g., that stimulate an immune response, e.g., a T cell response, e.g., expression and/or secretion of one or more immune mediators). In some embodiments, methods of the disclosure identify one or more polypeptides of interest as antigens or potential antigens that have minimal or no effect on an immune response (e.g., expression and/or secretion of one or more immune mediators). In some embodiments, methods of the disclosure identify one or more polypeptides of interest as inhibitory and/or suppressive antigens (e.g., that inhibit, suppress, down- regulate, impair, and/or prevent an immune response, e.g., a T cell response, e.g., expression and/or secretion of one or more immune mediators). In some embodiments, methods of the disclosure identify one or more polypeptides of interest as autoantigens or antigens derived from pathogens. In some embodiments, methods of the disclosure identify one or more polypeptides of interest as tumor antigens or potential tumor antigens, e.g, tumor specific antigens (TSAs, or neoantigens), tumor associated antigens (TAAs), or cancer/testis antigens (CT As).

[0145] In some embodiments, a polypeptide of interest is a putative antigen, and methods and compositions described herein can be used to identify and/or detect immune responses to one or more putative antigens. For example, members of a library include (e.g., internally express or carry) putative antigens (e.g., a polypeptide previously identified (e.g., by a third party) as an antigen, e.g., identified as an antigen using a method other than a method of the present disclosure). In some embodiments, a putative antigen is a tumor antigen described herein. In some such embodiments, such libraries can be used to assess whether and/or the extent to which such putative antigen mediates an immune response. In some embodiments, methods of the disclosure identify one or more putative antigens as stimulatory antigens. In some embodiments, methods of the disclosure identify one or more putative antigens as antigens that have minimal or no effect on an immune response. In some embodiments, methods of the disclosure identify one or more putative antigens as inhibitory and/or suppressive antigens.

[0146] In some embodiments, a polypeptide of interest is a pre-selected antigen, and methods and compositions described herein can be used to identify and/or detect immune responses to one or more pre-selected antigens. For example, in some embodiments, members of a library include (e.g., internally express or carry) one or more polypeptides identified as antigens using a method of the present disclosure and/or using a method other than a method of the present disclosure. In some such embodiments, such libraries can be used to assess whether and/or the extent to which such antigens mediate an immune response by an immune cell from one or more subjects to obtain one or more response profiles described herein. In some embodiments, methods of the disclosure identify one or more pre-selected antigens as stimulatory antigens for one or more subjects. In some embodiments, methods of the disclosure identify one or more pre-selected antigens as antigens that have minimal or no effect on an immune response for one or more subjects. In some embodiments, methods of the disclosure identify one or more pre-selected antigens as inhibitory and/or suppressive antigens for one or more subjects.

[0147] In some embodiments, a polypeptide of interest is a known antigen, and methods and compositions described herein can be used to identify and/or detect immune responses to such one or more known antigens. For example, in some embodiments, members of a library include (e.g., internally express or carry) one or more polypeptides identified as an antigen using a method of the present disclosure and/or using a method other than a method of the present disclosure. In some such embodiments, such libraries can be used to assess whether and/or the extent to which such antigens mediate an immune response by an immune cell from one or more subjects to obtain one or more response profiles described herein. In some embodiments, methods of the disclosure identify one or more known antigens as stimulatory antigens for one or more subjects. In some embodiments, methods of the disclosure identify one or more known antigens as antigens that have minimal or no effect on an immune response for one or more subjects. In some embodiments, methods of the disclosure identify one or more known antigens as inhibitory and/or suppressive antigens for one or more subjects.

[0148] In some embodiments, a polypeptide of interest is a potential antigen (e.g., an autoantigen, a tumor antigen, an antigen identified from a pathogen/infectious agent, or a tissuespecific or non-specific antigen, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue), and methods and compositions described herein can be used to identify and/or detect immune responses to one or more potential antigens.

[0149] For example, in some embodiments, members of a library include (e.g., internally express or carry) one or more polypeptides identified as being of interest, e.g., encoding autoantigens associated with an autoimmune disease, using a method of the present disclosure and/or using a method other than a method of the present disclosure. In some such embodiments, such libraries can be used to assess whether and/or the extent to which such polypeptides mediate an immune response by an immune cell from one or more subjects (e.g., a subject who has autoimmunity and/or a control subject) to obtain one or more response profdes described herein. In some embodiments, methods of the disclosure identify one or more polypeptides as stimulatory antigens for one or more subjects. In some embodiments, methods of the disclosure identify one or more polypeptides as antigens that have minimal or no effect on an immune response for one or more subjects. In some embodiments, methods of the disclosure identify one or more polypeptides as inhibitory and/or suppressive antigens for one or more subjects.

Antigens

[0150] Polypeptides of interest used in methods and systems described herein include antigens and potential antigens, e.g. , autoantigens, tumor antigens, antigens identified from infectious agents/pathogens, and tissue-specific or non-specific antigens, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue.

[0151] Exemplary antigens are provided in the accompanying list of sequences. In some embodiments, an antigen comprises a variant of an amino acid sequence of an antigen provided in the accompanying list of sequences (e.g., a sequence that is at least about 85%, 90%, 95%, 96%, 97% 98%, 99% identical to an amino acid sequence provided in the accompanying list of sequences) and/or a sequence that includes a mutation, deletion, and/or insertion of at least one amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acids) relative to an amino acid sequence provided in the accompanying list of sequences).

Tumor Antigens

[0152] Polypeptides of interest used in methods and systems described herein include tumor antigens amd potential tumor antigens, e.g., tumor specific antigens (TSAs, or neoantigens), tumor associated antigens (TAAs), and/or cancer/testis antigens (CT As). Exemplary tumor antigens include, e.g., MART-l/MelanA (MART-I or MLANA), gplOO (Pmel 17 or SILV), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3 (also known as HIP8), BAGE, GAGE-1, GAGE -2, pl5, Calcitonin, Calretinin, Carcinoembryonic antigen (CEA), Chromogranin, Cytokeratin, Desmin, Epithelial membrane protein (EMA), Factor VIII, Glial fibrillary acidic protein (GFAP), Gross cystic disease fluid protein (GCDFP-15), HMB-45, Human chorionic gonadotropin (hCG), inhibin, lymphocyte marker, MART- 1 (Melan-A), Myo DI, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase (PLAP), prostate-specific antigen, PTPRC (CD45), SI 00 protein, smooth muscle actin (SMA), synaptophysin, thyroglobulin, thyroid transcription factor-1, Tumor M2- PK, vimentin, p53, Ras, HER-2/neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens (e.g., EBNA1), human papillomavirus (HPV) antigen E6 or E7 (HPV E6 or HPV E7), TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO-1 (also known as CTAG1B), erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein (AFP), beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB/70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2 binding protein\cyclophilin C- associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ra2, FRa, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalyl cyclase C, MUC-1, CFC1B, integrin alpha 3 chain (of a3bl, a laminin receptor chain), TPS, CD19, CD20, CD22, CD30, CD31, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CD34, CD99, CD117, CD80, CD28, CD13, CD15, CD25, CD10, CLL-1/CLEC12A, ROR1, Glypican 3 (GPC3), Mesothelin, CD33/IL3Ra, c-Met, PSCA, PSMA, Glycolipid F77, EGFRvIII, BCMA, GD-2, PSAP, prostein (also known as P501S), PSMA, Survivin (also known as BIRC5), and MAGE-A3, MAGEA2, MAGEA4, MAGEA6, MAGEA9, MAGEA10, MAGEA12, BIRC5, CDH3, CEACAM3, CGB_isoform2, ELK4, ERBB2, HPSE1, HPSE2, KRAS_isoforml, KRAS_isoform2, MUC1, SMAD4, TERT, 2. TERT.3, TGFBR2, EGAG9_isoforml, TP53, CGB isoforml, IMPDH2, LCK, angiopoietin-1 (Angl) (also known as ANGPT1), XIAP (also known as BIRC4), galectin-3 (also known as LGALS3), VEGF-A (also known as VEGF), ATP6S1 (also known as ATP6AP1), MAGE- Al, cIAP-1 (also known as BIRC2), macrophage migration inhibitory factor (MIF), galectin-9 (also known as LGALS9), progranulin PGRN (also known as granulin), OGFR, MLIAP (also known as BIRC7), TBX4 (also known as ICPPS, SPS or T-Box4), secretory leukocyte protein inhibitor (Slpi) (also known as antileukoproteinase), Ang2 (also known as ANGPT2), galectin-1 (also known as LGALS1), TRP-2 (also known as DCT), hTERT (telomerase reverse transcriptase) tyrosinase -related protein 1 (TRP-1, TYRP1), NOR-90/UBF-2 (also known as UBTF), LGMN, SPA17, PRTN3, TRRAP 1, TRRAP 2, TRRAP 3, TRRAP 4, MAGEC2, PRAME, SOXIO, RAC1, HRAS, GAGE4, AR, CYP1B1, MMP8, MMP9, TYR, PDGFRB, KLK3, PAX3, PAX5, ST3GAL5, PLAC1, RhoC, MYCN, REG3A, CSAG2, CTAG2-la, CTAG2-lb, PAGE4, BRAF, GRM3, ERBB4, KIT, MAPK1, MFI2, SART3, ST8SIA1, WDR46, AKAP-4, RGS5, FOSL1, PRM2, ACRBP, CTCFL, CSPG4, CCNB1, MSLN, WT1, SSX2, KDR, ANKRD30A, MAGED1, MAP3K9, XAGE1B, PREX2, CD276, TEK, AIM1, ALK, FOLH1, GRIN2A MAP3K5 and one or more isoforms of any preceding tumor antigens. Exemplary tumor antigens are provided in the accompanying list of sequences. In some embodiments, a tumor antigen comprises a variant of an amino acid sequence provided in the accompanying list of sequences (e.g., a sequence that is at least about 85%, 90%, 95%, 96%, 97% 98%, 99% identical to an amino acid sequence provided in the accompanying list of sequences and/or a sequence that includes a mutation, deletion, and/or insertion of at least one amino acid (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acids) relative to an amino acid sequence provided in the accompanying list of sequences).

[0153] Tumor specific antigens (TSAs, or neoantigens) are tumor antigens that are not encoded in normal host genome (see, e.g., Yarchoan et al., Nat. Rev. Cancer. 2017 Feb 24. doi: 10.1038/nrc.2016.154; Gubin et al., J. Clin. Invest. 125:3413-3421 (2015)). In some embodiments, TSAs arise from somatic mutations and/or other genetic alterations. In some embodiments, TSAs arise from missense or in-frame mutations. In some embodiments, TSAs arise from frame-shift mutations or loss-of-stop-codon mutations. In some embodiments, TSAs arise from insertion or deletion mutations. In some embodiments, TSAs arise from duplication or repeat expansion mutations. In some embodiments, TSAs arise from splice variants or improper splicing. In some embodiments, TSAs arise from gene fusions. In some embodiments, TSAs arise from translocations. In some embodiments, TSAs include oncogenic viral proteins. For example, as with Merkel cell carcinoma (MCC) associated with the Merkel cell polyomavirus (MCPy V) and cancers of the cervix, oropharynx and other sites associated with the human papillomavirus (HPV), TSAs include proteins encoded by viral open reading frames. For purposes of this disclosure, the terms “mutation” and “mutations” encompass all mutations and genetic alterations that may give rise to an antigen encoded in the genome of a cancer or tumor cell of a subject, but not in a normal or non-cancerous cell of the same subject. In some embodiments, TSAs are specific (personal) to a subject. In some embodiments, TSAs are shared by more than one subject, e.g., less than 1%, 1-3%, 1-5%, 1-10%, or more of subjects suffering from a cancer. In some embodiments, TSAs shared by more than one subject may be known or pre-selected.

[0154] In some embodiments, a TSA is encoded by an open reading frame from a virus. For example, a library can be designed to express polypeptides from one of the following viruses: an immunodeficiency virus (e.g., a human immunodeficiency virus (HIV), e.g, HIV-1, HIV-2), a hepatitis virus (e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis A virus, non -A and non-B hepatitis virus), a herpes virus (e.g., herpes simplex virus type I (HSV-1), HSV-2, Varicellazoster virus, Epstein Barr virus, human cytomegalovirus, human herpesvirus 6 (HHV-6), HHV-7, HHV-8), a poxvirus (e.g., variola, vaccinia, monkeypox, Molluscum contagiosum virus), an influenza virus, a human papilloma virus, adenovirus, rhinovirus, coronavirus, respiratory syncytial virus, rabies virus, coxsackie virus, human T cell leukemia virus (types I, II and III), parainfluenza virus, paramyxovirus, poliovirus, rotavirus, rhinovirus, rubella virus, measles virus, mumps virus, adenovirus, yellow fever virus, Norwalk virus, West Nile virus, a Dengue virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), bunyavirus, Ebola virus, Marburg virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Japanese encephalitis virus, St. Louis encephalitis virus, Junin virus, Lassa virus, and Lymphocytic choriomeningitis virus. Libraries for other viruses can also be produced and used according to methods described herein.

[0155] Tumor specific antigens are known in the art, any of which can be used in methods described herein. In some embodiments, gene sequences encoding polypeptides that are potential or putative neoantigens are determined by sequencing the genome and/or exome of tumor tissue and healthy tissue from a subject having cancer using next generation sequencing technologies. In some embodiments, genes that are selected based on their frequency of mutation and ability to encode a potential or putative neoantigen are sequenced using next-generation sequencing technology. Nextgeneration sequencing applies to genome sequencing, genome resequencing, transcriptome profiling (RNA-Seq), DNA-protein interactions (ChlP-sequencing), and epigenome characterization (de Magalhaes et al. (2010) Ageing Research Reviews 9 (3): 315-323; Hall N (2007) J. Exp. Biol. 209 (Pt 9): 1518-1525; Church (2006) Sci. Am. 294 (1): 46-54; ten Bosch et al. (2008) Journal of Molecular Diagnostics 10 (6): 484-492; Tucker T et al. (2009) The American Journal of Human Genetics 85 (2): 142-154). Next-generation sequencing can be used to rapidly reveal the presence of discrete mutations such as coding mutations in individual tumors, e.g., single amino acid changes (e.g., missense mutations, in-frame mutations) or novel stretches of amino acids generated by frame-shift insertions, deletions, gene fusions, read-through mutations in stop codons, duplication or repeat expansion mutations, and translation of splice variants or improperly spliced introns, and translocations (e.g., “neoORFs”).

[0156] Another method for identifying potential or putative neoantigens is direct protein sequencing. Protein sequencing of enzymatic digests using multidimensional MS techniques (MSn) including tandem mass spectrometry (MS/MS)) can also be used to identify neoantigens. Such proteomic approaches can be used for rapid, highly automated analysis (see, e.g., Gevaert et al., Electrophoresis 21 : 1145-1154 (2000)). High-throughput methods for de novo sequencing of unknown proteins can also be used to analyze the proteome of a subject’s tumor to identify expressed potential or putative neoantigens. For example, meta shotgun protein sequencing may be used to identify expressed potential or putative neoantigens (see e.g., Guthals et al. (2012) Molecular and Cellular Proteomics 11(10): 1084-96).

[0157] Potential or putative neoantigens may also be identified using MHC multimers to identify neoantigen-specific T cell responses. For example, high-throughput analysis of neoantigenspecific T cell responses in patient samples may be performed using MHC tetramer -based screening techniques (see e.g., Hombrink et al. (2011) PLoS One; 6(8): e22523; Hadrup et al. (2009) Nature Methods, 6(7):520-26; van Rooij et al. (2013) Journal of Clinical Oncology, 31:1-4; and Heemskerk et al. (2013) EMBO Journal, 32(2): 194-203). [0158] In some embodiments, one or more known or pre-selected tumor specific antigens, or one or more potential or putative tumor specific antigens identified using one of these methods, can be included in a library described herein.

[0159] Tumor associated antigens (TAAs) include proteins encoded in a normal genome (see, e.g., Ward et al., Adv. Immunol. 130:25-74 (2016)). In some embodiments, TAAs are either normal differentiation antigens or aberrantly expressed normal proteins. Overexpressed normal proteins that possess growth/survival -promoting functions, such as Wilms tumor 1 (WT1) (Ohminami et al., Blood 95:286-293 (2000)) or Her2/neu (Kawashima et al., Cancer Res. 59:431-435 (1999)), are TAAs that directly participate in the oncogenic process. Post-translational modifications, such as phosphorylation, of proteins may also lead to formation of TAAs (Doyle, J. Biol. Chem. 281:32676- 32683 (2006); Cobbold, Sci. Transl. Med. 5:203ral25 (2013)). TAAs are generally shared by more than one subject, e.g, less than 1%, 1-3%, 1-5%, 1-10%, 1-20%, or more of subjects suffering from a cancer. In some embodiments, TAAs are known or pre-selected tumor antigens. In some embodiments, with respect to an individual subject, TAAs are potential or putative tumor antigens. Cancer/testis antigens (CTAs) are expressed by various tumor types and by reproductive tissues (for example, testes, fetal ovaries and trophoblasts) but have limited or no detectable expression in other normal tissues in the adult and are generally not presented on normal reproductive cells, because these tissues do not express MHC class I molecules (see, e.g, Coulie et al., Nat. Rev. Cancer 14:135-146 (2014); Simpson et al., Nat. Rev. Cancer 5:615-625 (2005); Scanlan et al., Immunol. Rev. 188:22-32 (2002)).

[0160] Polypeptides of interest used in methods and systems described herein include tissuespecific or non-specific antigens identified from a ceil or tissue which is a target of an autoimmune response. Polypeptides of interest used in methods and systems described herein include antigens identified from a healthy cell or tissue in a subject.

Antigens to Pathogens/Infectious Agents

[0161] Polypeptides of interest used in methods and systems described herein include antigens to pathogens and infectious agents. Exemplary pathogens include viruses, bacteria, fungi, protozoa, or helminths that infect humans.

[0162] In some embodiments, an antigen is identified from a viruses such as immunodeficiency virus (e.g., a human immunodeficiency virus (HIV), e.g, HIV-1, HIV-2), a hepatitis virus (e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis A virus, non-A and non-B hepatitis virus), a herpes virus (e.g., herpes simplex virus type I (HSV-1), HSV-2, Varicellazoster virus, Epstein Barr virus, human cytomegalovirus, human herpesvirus 6 (HHV-6), HHV-7, HHV-8), a poxvirus (e.g., variola, vaccinia, monkeypox, Molluscum contagiosum virus), an influenza virus, a human papilloma virus, adenovirus, rhinovirus, coronavirus, respiratory syncytial virus, rabies virus, coxsackie virus, human T-cell leukemia virus (types I, II and III), parainfluenza virus, paramyxovirus, poliovirus, rotavirus, rhinovirus, rubella virus, measles virus, mumps virus, adenovirus, yellow fever virus, Norwalk virus, West Nile virus, a Dengue virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), bunyavirus, Ebola virus, Marburg virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Japanese encephalitis virus, St. Louis encephalitis virus, Junin virus, Lassa virus, and Lymphocytic choriomeningitis virus. Libraries for other viruses can also be produced and used according to methods described herein.

[0163] In some embodiments, an antigen is identified from a bacteria (e.g., from a bacterial pathogen). In some embodiments, the bacterial pathogen is an intracellular pathogen. In some embodiments, the bacterial pathogen is an extracellular pathogen. Examples of bacterial pathogens include bacteria from the following genera and species: Chlamydia (e.g., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis), Legionella (e.g., Legionella pneumophila), Listeria (e.g., Listeria monocytogenes), Rickettsia (e.g., R. australis, R. rickettsii, R. akari, R. conorii, R. sibirica, R. japonica, R. africae, R. typhi, R. prowazekii), Actinobacter (e.g., Actinobacter baumannii), Bordetella (e.g., Bordetella pertussis), Bacillus (e.g., Bacillus anthracis, Bacillus cereus), Bacteroides (e.g., Bacteroides fragilis), Bartonella (e.g., Bartonella henselae), Borrelia (e.g., Borrelia burgdorferi), Brucella (e.g., Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis), Campylobacter (e.g., Campylobacter jejuni), Clostridium (e.g., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani), Corynebacterium (e.g., Corynebacterium diphtheriae, Corynebacterium amycolatum), Enterococcus (e.g., Enterococcus faecalis, Enterococcus faecium), Escherichia (e.g., Escherichia coli), Francisella (e.g., Francisella tularensis), Haemophilus (e.g., Haemophilus influenzae), Helicobacter (e.g., Helicobacter pylori), Klebsiella (e.g., Klebsiella pneumoniae), Leptospira (e.g., Leptospira interrogans), Mycobacteria (e.g., Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma (e.g., Mycoplasma pneumoniae), Neisseria (e.g., Neisseria gonorrhoeae, Neisseria meningitidis), Pseudomonas (e.g., Pseudomonas aeruginosa), Salmonella (e.g., Salmonella typhi, Salmonella typhimurium, Salmonella enterica), Shigella (e.g., Shigella dysenteriae, Shigella sonnei), Staphylococcus (e.g., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus), Streptococcus (e.g., Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes), Treponoma (e.g., Treponoma pallidum), Vibrio (e.g., Vibrio cholerae, Vibrio vulnificus), and Yersinia (e.g., Yersinia pestis). Libraries for other bacteria can also be produced and used according to methods described herein.

[0164] In some embodiments, an antigen is identified from a protozoan. Examples of protozoal pathogens include the following organisms: Cryptosporidium parvum, Entamoeba (e.g., Entamoeba histolytica), Giardia (e.g., Giardia lambda), Leishmania (e.g., Leishmania donovani), Plasmodium spp. (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae), Toxoplasma (e.g., Toxoplasma gondii), Trichomonas (e.g., Trichomonas vaginalis), and Trypanosoma (e.g., Trypanosoma brucei, Trypanosoma cruzi). Libraries for other protozoa can also be produced and used according to methods described herein.

[0165] In some embodiments, an antigen is identified from a fungus. Examples of fungal pathogens include the following: Aspergillus, Candida (e.g., Candida albicans), Coccidiodes (e.g., Coccidiodes immitis), Cryptococcus (e.g., Cryptococcus neoformans), Histoplasma (e.g, Histoplasma capsulatum), and Pneumocystis (e.g, Pneumocystis carinii). Libraries for other fungi can also be produced and used according to methods described herein.

[0166] In some embodiments, an antigen is identified from a helminth. Examples of helminthic pathogens include Ascaris lumbricoides, Ancylostoma, Clonorchis sinensis, Dracuncula medinensis, Enterobius vermicularis, Filaria, Onchocerca volvulus, Loa loa, Schistosoma, Strongyloides, Trichuris trichura, and Trichinella spiralis. Libraries for other helminths can also be produced and used according to methods described herein.

[0167] Sequence information for genomes and ORFs for infectious agents is publicly available. See, e.g, the Entrez Genome Database (URL: ncbi.nlm.nih.gov/sites/entrez?db=Genome&itool=toolbar) and the ERGO™ Database (URL: igweb.integratedgenomics.com/ERGO_supplement/genomes.html), the Genomes Online Database (GOLD) (URL: genomesonline.org) (Liolios et al., Nucleic Acids Res. 1; 34(Database issue) :D332-4, 2006).

Library Screens

Human Cells for Antigen Presentation

[0168] The present disclosure provides, inter alia, compositions and methods for identifying antigens recognized by human immune cells. Human antigen presenting cells express ligands for antigen receptors and other immune activation molecules on human lymphocytes. Given differences in MHC peptide binding specificities and antigen processing enzymes between species, antigens processed and presented by human cells are more likely to be physiologically relevant human antigens in vivo than antigens identified in non-human systems. Accordingly, methods of identifying these antigens employ human cells to present candidate antigen polypeptides. Any human cell that internalizes library members and presents polypeptides expressed by the library members on MHC molecules can be used as an antigen presenting cell according to the present disclosure. In some embodiments, human cells used for antigen presentation are primary human cells. The cells can include peripheral blood mononuclear cells (PBMC) of a human. In some embodiments, peripheral blood cells are separated into subsets (e.g., subsets comprising dendritic cells, macrophages, monocytes, B cells, or combinations thereof) prior to use in an antigen presentation assay, in some embodiments, a subset of cells that expresses MHC class II is selected from peripheral blood. In one example, a cell population including dendritic cells is isolated from peripheral blood. In some embodiments, a subset of dendritic cells is isolated (e.g., plasmacytoid, myeloid, or a subset thereof). Human dendritic cell markers include CDlc, CDla, CD303, CD304, CD141, and CD209. Cells can be selected based on expression of one or more of these markers (e.g., cells that express CD303, CDlc, and CD141).

[0169] Dendritic cells can be isolated by positive selection from peripheral blood using commercially available kits (e.g., from Miltenyi Biotec Inc.). In some embodiments, the dendritic cells are expanded ex vivo prior to use in an assay. Dendritic cells can also be produced by culturing peripheral blood cells under conditions that promote differentiation of monocyte precursors into dendritic cells in vitro. These conditions typically include culturing the cells in the presence of cytokines such as GM-CSF and IL-4 (see, e.g., Inaba et al., Isolation of dendritic cells, Curr. Protoc. Immunol. May; Chapter 3: Unit 3.7, 2001). Procedures for in vitro expansion of hematopoietic stem and progenitor cells (e.g., taken from bone marrow or peripheral blood), and differentiation of these cells into dendritic cells in vitro, is described in U.S. Pat. No. 5,199,942, and U.S. Pat.

Pub. 20030077263. Briefly, CD34⁺ hematopoietic stem and progenitor cells are isolated from peripheral blood or bone marrow and expanded in vitro in culture conditions that include one or more of Flt3-L, IL-1, IL-3, and c-kit ligand.

[0170] In some embodiments, immortalized cells that express human MHC molecules (e.g. , human cells, or non-human cells that are engineered to express human MHC molecules) are used for antigen presentation. For example, assays can employ COS cells transfected with human MHC molecules or HeLa cells.

[0171] In some embodiments, both the antigen presenting cells and immune cells used in the method are derived from the same subject (e.g., autologous T cells and APC are used). In these embodiments, it can be advantageous to sequentially isolate subsets of cells from peripheral blood of the subject, to maximize the yield of cells available for assays. For example, one can first isolate CD4⁺ and CD8⁺ T cell subsets from the peripheral blood. Next, dendritic cells (DC) are isolated from the T cell-depleted cell population. The remaining T- and DC-depleted cells are used to supplement the DC in assays, or are used alone as antigen presenting cells. In some embodiments, DC are used with T- and DC-depleted cells in an assay, at a ratio of 1:2, 1:3, 1:4, or 1:5. In some embodiments, the antigen presenting cells and immune cells used in the method are derived from different subjects (e.g., heterologous T cells and APC are used).

[0172] Antigen presenting cells can be isolated from sources other than peripheral blood. For example, antigen presenting cells can be taken from a mucosal tissue (e.g., nose, mouth, bronchial tissue, tracheal tissue, the gastrointestinal tract, the genital tract (e.g., vaginal tissue), or associated lymphoid tissue), peritoneal cavity, lymph nodes, spleen, bone marrow, thymus, lung, liver, kidney, neuronal tissue, endocrine tissue, or other tissue, for use in screening assays. In some embodiments, cells are taken from a tissue that is the site of an active immune response (e.g., an ulcer, sore, or abscess). Cells may be isolated from tissue removed surgically, via lavage, or other means.

[0173] Antigen presenting cells useful in methods described herein are not limited to “professional” antigen presenting cells. In some embodiments, non-professional antigen presenting cells can be utilized effectively in the practice of methods of the present disclosure. Non-professional antigen presenting cells include fibroblasts, epithelial cells, endothelial cells, neuronal/glial cells, lymphoid or myeloid cells that are not professional antigen presenting cells (e.g., T cells, neutrophils), muscle cells, liver cells, and other types of cells.

[0174] Antigen presenting cells are cultured with library members that express a polypeptide of interest (and, if desired, a cytolysin polypeptide) under conditions in which the antigen presenting cells internalize, process and present polypeptides expressed by the library members on MHC molecules. In some embodiments, library members are killed or inactivated prior to culture with the antigen presenting cells. Cells or viruses can be inactivated by any appropriate agent (e.g., fixation with organic solvents, irradiation, freezing). In some embodiments, the library members are cells that express ORFs linked to a tag (e.g., a tag which comprises one or more known T cell epitopes) or reporter protein, expression of which has been verified prior to the culturing.

[0175] In some embodiments, antigen presenting cells are incubated with library members at 37°C for between 30 minutes and 5 hours (e.g., for 45 min. to 1.5 hours). After the incubation, the antigen presenting cells can be washed to remove library members that have not been internalized. In certain embodiments, the antigen presenting cells are non-adherent, and washing requires centrifugation of the cells. The washed antigen presenting cells can be incubated at 37°C for an additional period of time (e.g., 30 min. to 2 hours) prior to exposure to lymphocytes, to allow antigen processing. In some embodiments, it is desirable to fix and kill the antigen presenting cells prior to exposure to lymphocytes (e.g., by treating the cells with 1% paraformaldehyde).

[0176] The antigen presenting cell and library member numbers can be varied, so long as the library members provide quantities of polypeptides of interest sufficient for presentation on MHC molecules. In some embodiments, antigen presenting cells are provided in an array, and are contacted with sets of library cells, each set expressing a different polypeptide of interest. In certain embodiments, each location in the array includes 1 x 10³ - 1 x 10⁶ antigen presenting cells, and the cells are contacted with 1 x 10³ - 1 x 10⁸ library cells which are bacterial cells.

[0177] In any of the embodiments described herein, antigen presenting cells can be freshly isolated, maintained in culture, and/or thawed from frozen storage prior to incubation with library cells, or after incubation with library cells. Human Lymphocytes

[0178] In methods of the present disclosure, human lymphocytes are tested for antigenspecific reactivity to antigen presenting cells, e.g. , antigen presenting cells that have been incubated with libraries expressing polypeptides of interest as described above. The methods of the present disclosure permit rapid identification of human antigens using pools of lymphocytes isolated from an individual, or progeny of the cells. The detection of antigen-specific responses does not rely on laborious procedures to isolate individual T cell clones. In some embodiments, the human lymphocytes are primary lymphocytes. In some embodiments, human lymphocytes are NKT cells, gamma-delta T cells, or NK cells. Just as antigen presenting cells may be separated into subsets prior to use in antigen presentation assays, a population of lymphocytes having a specific marker or other feature can be used. In some embodiments, a population of T lymphocytes is isolated. In some embodiments, a population of CD4⁺ T cells is isolated. In some embodiments, a population of CD8⁺ T cells is isolated. CD8⁺ T cells recognize peptide antigens presented in the context of MHC class I molecules. Thus, in some embodiments, the CD8⁺ T cells are used with antigen presenting cells that have been exposed to library host cells that co-express a cytolysin polypeptide, in addition to a polypeptide of interest. T cell subsets that express other cell surface markers may also be isolated, e.g, to provide cells having a particular phenotype. These include CLA (for skin-homing T cells), CD25, CD30, CD69, CD154 (for activated T cells), CD45RO (for memory T cells), CD294 (for Th2 cells), y/8 TCR-expressing cells, CD3 and CD56 (forNK T cells). Other subsets can also be selected.

[0179] Lymphocytes can be isolated, and separated, by any means known in the art (e.g., using antibody -based methods such as those that employ magnetic bead separation, panning, or flow cytometry). Reagents to identify and isolate human lymphocytes and subsets thereof are well known and commercially available.

[0180] Lymphocytes for use in methods described herein can be isolated from peripheral blood mononuclear cells, or from other tissues in a human. In some embodiments, lymphocytes are taken from tumors, lymph nodes, a mucosal tissue (e.g., nose, mouth, bronchial tissue, tracheal tissue, the gastrointestinal tract, the genital tract (e.g., vaginal tissue), or associated lymphoid tissue), peritoneal cavity, spleen, thymus, lung, liver, kidney, neuronal tissue, endocrine tissue, peritoneal cavity, bone marrow, or other tissues. In some embodiments, cells are taken from a tissue that is the site of an active immune response (e.g., an ulcer, sore, or abscess). Cells may be isolated from tissue removed surgically, via lavage, or other means.

[0181] Lymphocytes taken from an individual can be maintained in culture or frozen until use in antigen presentation assays. In some embodiments, freshly isolated lymphocytes can be stimulated in vitro by antigen presenting cells exposed to library cells as described above. In some embodiments, these lymphocytes exhibit detectable stimulation without the need for prior non-antigen specific expansion. However, primary lymphocytes also elicit detectable antigen-specific responses when first stimulated non-specifically in vitro. Thus, in some embodiments, lymphocytes are stimulated to proliferate in vitro in a non-antigen specific manner, prior to use in an antigen presentation assay. Lymphocytes can also be stimulated in an antigen-specific manner prior to use in an antigen presentation assay. In some embodiments, cells are stimulated to proliferate by a library (e.g., prior to use in an antigen presentation assay that employs the library). Expanding cells in vitro provides greater numbers of cells for use in assays. Primary T cells can be stimulated to expand, e.g., by exposure to a polyclonal T cell mitogen, such as phytohemagglutinin or concanavalin, by treatment with antibodies that stimulate proliferation, or by treatment with particles coated with the antibodies. In some embodiments, T cells are expanded by treatment with anti-CD2, anti-CD3, and anti-CD28 antibodies. In some embodiments, T cells are expanded by treatment with interleukin-2 (IL-2). In some embodiments, lymphocytes are thawed from frozen storage and expanded (e.g., stimulated to proliferate, e.g., in a non-antigen specific manner or in an antigen-specific manner) prior to contacting with antigen presenting cells. In some embodiments, lymphocytes are thawed from frozen storage and are not expanded prior to contacting with antigen presenting cells. In some embodiments, lymphocytes are freshly isolated and expanded (e.g., stimulated to proliferate, e.g., in a non-antigen specific manner or in an antigen-specific manner) prior to contacting with antigen presenting cells.

Antigen Presentation Assays

[0182] In antigen presentation assays, T cells are cultured with antigen presenting cells prepared according to the methods described above, under conditions that permit T cell recognition of peptides presented by MHC molecules on the antigen presenting cells. In some embodiments, T cells are incubated with antigen presenting cells at 37°C for between 12-48 hours (e.g., for 24 hours). In some embodiments, T cells are incubated with antigen presenting cells at 37°C for 3, 4, 5, 6, 7, or 8 days. Numbers of antigen presenting cells and T cells can be varied. In some embodiments, the ratio of T cells to antigen presenting cells in a given assay is 1: 10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1, 20:1, 25:1, 30:1, 32:1, 35:1 or 40:1. In some embodiments, antigen presenting cells are provided in an array (e.g., in a 96-well plate), wherein cells in each location of the array have been contacted with sets of library cells, each set including a different polypeptide of interest. In certain embodiments, each location in the array includes 1 x 10³ - 1 x 10⁶ antigen presenting cells, and the cells are contacted with 1 x 10³ - 1 x 10⁶ T cells.

[0183] After T cells have been incubated with antigen presenting cells, cultures are assayed for activation. Lymphocyte activation can be detected by any means known in the art, e.g. , T cell proliferation, phosphorylation or dephosphorylation of a receptor, calcium flux, cytoskeletal rearrangement, increased or decreased expression and/or secretion of immune mediators such as cytokines or soluble mediators, increased or decreased expression of one or more cell surface markers. In some embodiments, culture supernatants are harvested and assayed for increased and/or decreased expression and/or secretion of one or more polypeptides associated with activation, e.g., a cytokine, soluble mediator, cell surface marker, or other immune mediator. In some embodiments, the one or more cytokines are selected from TRAIL, IFN-gamma, IL-12p70, IL-2, TNF-alpha, MIP1- alpha, MIPl-beta, CXCL9, CXCL10, MCP1, RANTES, IL-1 beta, IL-4, IL-6, IL-8, IL-9, IL-10, IL- 13, IL-15, CXCL11, IL-3, IL-5, IL-17, IL-18, IL-21, IL-22, IL-23 A, IL-24, IL-27, IL-31, IL-32, TGF- beta, CSF, GM-CSF, TRANCE (also known as RANK L), MIP3-alpha, and fractalkine. In some embodiments, the one or more soluble mediators are selected from granzyme A, granzyme B, sFas, sFasL, perforin, and granulysin. In some embodiments, the one or more cell surface markers are selected from CD107a, CD107b, CD25, CD69, CD45RA, CD45RO, CD137 (4-1BB), CD44, CD62L, CD27, CCR7, CD154 (CD40L), KLRG-1, CD71, HLA-DR, CD122 (IL-2RB), CD28, IL7Ra (CD127), CD38, CD26, CD134 (OX-40), CTLA-4 (CD152), LAG-3, TIM-3 (CD366), CD39, PD1 (CD279), FoxP3, TIGIT, CD 160, BTLA, 2B4 (CD244), and KLRG1. Cytokine secretion in culture supernatants can be detected, e.g., by ELISA, bead array, e.g., with a Luminex® analyzer. Cytokine production can also be assayed by RT-PCR of mRNA isolated from the T cells, or by ELISpot analysis of cytokines released by the T cells. In some embodiments, proliferation of T cells in the cultures is determined (e.g., by detecting ³H thymidine incorporation). In some embodiments, target cell lysis is determined (e.g., by detecting T cell dependent lysis of antigen presenting cells labeled with Na2 ⁵¹CrO4). Target cell lysis assays are typically performed with CD8⁺ T cells. Protocols for these detection methods are known. See, e.g., Current Protocols In Immunology, John E. Coligan et al. (eds), Wiley and Sons, New York, N.Y., 2007. One of skill in the art understands that appropriate controls are used in these detection methods, e.g., to adjust for non-antigen specific background activation, to confirm the presenting capacity of antigen presenting cells, and to confirm the viability of lymphocytes.

[0184] In some embodiments, antigen presenting cells and lymphocytes used in the method are from the same individual. In some embodiments, antigen presenting cells and lymphocytes used in the method are from different individuals.

[0185] In some embodiments, antigen presentation assays are repeated using lymphocytes from the same individual that have undergone one or more previous rounds of exposure to antigen presenting cells, e.g, to enhance detection of responses, or to enhance weak initial responses. In some embodiments, antigen presentation assays are repeated using antigen presenting cells from the same individual that have undergone one or more previous rounds of exposure to a library, e.g, to enhance detection of responses, or to enhance weak initial responses. In some embodiments, antigen presentation assays are repeated using lymphocytes from the same individual that have undergone one or more previous rounds of exposure to antigen presenting cells, and antigen presenting cells from the same individual that have undergone one or more previous rounds of exposure to a library, e.g., to enhance detection of responses, or to enhance weak initial responses. In some embodiments, antigen presentation assays are repeated using antigen presenting cells and lymphocytes from different individuals, e.g., to identify antigens recognized by multiple individuals, or compare reactivities that differ between individuals.

Methods of Identifying Antigens

[0186] In some embodiments, lymphocytes are screened against antigen presenting cells that have been contacted with a library of cells whose members express or carry polypeptides of interest, and the lymphocytes are from an individual who has not been diagnosed with an autoimmune disease, overactive immune condition, or cancer, or who has not been exposed to an infectious agent/pathogen. In some embodiments, such lymphocytes are used to determine background (i.e., non-antigen- specific) reactivities. In some embodiments, such lymphocytes are used to identify antigens, reactivity to which exists in individuals who have not been diagnosed with an autoimmune disease, overactive immune condition, or cancer, or who have not been exposed to an infectious agent/pathogen.

[0187] Cells from multiple donors (e.g., multiple subjects who have an autoimmune disease, overactive immune condition, or cancer, or who have been exposed to an infectious agent/pathogen) can be collected and assayed in methods described herein. In some embodiments, cells from multiple donors are assayed in order to determine if a given antigen is reactive in a broad portion of the population, or to identify multiple antigens that can be later combined to produce an immunogenic composition that will be effective in a broad portion of the population.

[0188] Antigen presentation assays are useful in the context of both infectious and non- infectious diseases. The methods described herein are applicable to any context in which a rapid evaluation of human cellular immunity is beneficial. In some embodiments, antigenic reactivity to polypeptides that are differentially expressed by diseased cells (e.g. , cells that are the target of an autoimmune response, or tumor cells) is evaluated. Sets of nucleic acids differentially expressed by diseased cells have been identified using established techniques such as subtractive hybridization. Methods described herein can be used to identify antigens that were functional in a subject in which an immune response occurred. In other embodiments, methods are used to evaluate whether a subject has lymphocytes that react to an antigen or set of antigens.

[0189] In some embodiments, antigen presentation assays are used to examine reactivity to autoantigens in cells of an individual, e.g, an individual predisposed to, or suffering from, an autoimmune condition. Such methods can be used to provide diagnostic or prognostic indicators of the individual’s disease state, or to identify autoantigens. For these assays, in some embodiments, libraries that include an array of human polypeptides are prepared. In some embodiments, libraries that include polypeptides from infectious agents which are suspected of eliciting cross-reactive responses to autoantigens are prepared. For examples of antigens from infectious agents thought to elicit cross -re active autoimmune responses, see Barzilai et al., Curr Opin Rheumatol., 19(6):636-43, 2007; Ayada et al., Ann N Y Acad Sci., 1108:594-602, 2007; Drouin et al., Mol Immunol., 45(1): 180- 9, 2008; and Bach, J Autoimmun., 25 Suppl:74-80, 2005.

[0190] As discussed, the present disclosure includes methods in which polypeptides of interest are included in a library (e.g., expressed in library cells or carried in or on particles or beads). After members of the library are internalized by antigen presenting cells, the polypeptides of interest are proteolytically processed within the antigen presenting cells, and peptide fragments of the polypeptides are presented on MHC molecules expressed in the antigen presenting cells. The identity of the polypeptide that stimulates a human lymphocyte in an assay described herein can be determined from examination of the set of library cells that were provided to the antigen presenting cells that produced the stimulation. In some embodiments, it is useful to map the epitope within the polypeptide that is bound by MHC molecules to produce the observed stimulation. This epitope, or the longer polypeptide from which it is derived (both of which are referred to as an “antigen” herein) can form the basis for an immunogenic composition, or for an antigenic stimulus in future antigen presentation assays.

[0191] Methods for identifying peptides bound by MHC molecules are known. In some embodiments, epitopes are identified by generating deletion mutants of the polypeptide of interest and testing these for the ability to stimulate lymphocytes. Deletions that lose the ability to stimulate lymphocytes, when processed and presented by antigen presenting cells, have lost the peptide epitope. In some embodiments, epitopes are identified by synthesizing peptides corresponding to portions of the polypeptide of interest and testing the peptides for the ability to stimulate lymphocytes (e.g., in antigen presentation assays in which antigen presenting cells are pulsed with the peptides). Other methods for identifying MHC bound peptides involve lysis of the antigen presenting cells that include the antigenic peptide, affinity purification of the MHC molecules from cell lysates, and subsequent elution and analysis of peptides from the MHC (Falk, K. et al. Nature 351:290, 1991, and U.S. Pat. No. 5,989,565).

[0192] In other embodiments, it is useful to identify the clonal T cell receptors that have been expanded in response to the antigen. Clonal T cell receptors are identified by DNA sequencing of the T cell receptor repertoire (Howie et al, 2015 Sci Trans Med 7:301). By identifying TCR specificity and function, TCRs can be transfected into other cell types and used in functional studies or for novel immunotherapies.

T Cell Compositions for Adoptive Cell Therapy Overall Rationale

[0193] Certain methods of the disclosure are directed to stimulating and expanding a population of inhibitory antigen-specific T cells to make a highly effective, personalized or nonpersonalized, adoptive T cell therapy for patients suffering from an autoimmune disease or overactive immune condition. Identification and selection of inhibitory antigens (inhibigen) to stimulate and expand T cells ex vivo is achieved using ATLAS, an immune response profiling method that enables comprehensive screening of potential antigens. The inhibitory antigens used to stimulate and expand the T cells ex vivo may be patient-specific (personal), or may be shared by a cohort of patients, or may comprise both patient-specific (personal) and shared antigens.

Rationale for ATLAS as the Antigen Identification and Selection Method

[0194] The ATLAS method, as further described in WO 2010/002993, allows rapid, high- throughput identification of pre-existing, antigen-specific T cell responses without the use of in silico down-selection criteria. ATLAS eliminates many of the challenges associated with use of prediction tools for tumor or other antigen selection by providing the following advantages: /) it empirically identifies antigens using subjects’ T cells and professional and/or non-professional antigen presenting cells, e.g., monocyte-derived dendritic cells (MDDCs), instead of computer-based predictions that require validation; //) it comprehensively covers HLA specificities; Hi) it separately identifies antigens for both CD4⁺ and CD8⁺ T cell subsets; and iv) it facilitates antigen selection based on biologically relevant T cell responses.

[0195] To date, the ATLAS method has been used to profile T cell responses for multiple proteomic libraries, ranging from a few dozen to over 2,000 expressed genes from HSV-2, Streptococcus pneumoniae, Chlamydia trachomatis, Plasmodium falciparum, human papilloma virus, and Epstein-Barr virus. In oncology, ATLAS has also been used to screen putative neoantigens, oncoviral antigens, melanoma tumor-associated antigens, colorectal cancer-associated antigens, and lung tumor-associated antigens. In all cases, ATLAS has enabled comprehensive screening of potential antigens using autologous cells and identified targets of pre-existing stimulatory as well as inhibitory antigen-specific T cell responses.

Methods of Obtaining T cells

[0196] In certain embodiments of the disclosure, a source of T cells can first be obtained, e.g., from a subject. Non-limiting examples of subjects include humans, dogs, cats, mice, rats, and transgenic species thereof. As described herein, T cells or PBMCs enriched for or depleted of a certain population of T cells can be administered to a subject. Thus, the T cells will have an immunocompatibility relationship to a recipient subject, and any such relationship is contemplated for use according to the present disclosure. [0197] For example, the T cells can be syngeneic to a recipient subject. The term “syngeneic” refers to the state of deriving from, originating in, or being members of the same species that are genetically identical, particularly with respect to antigens or immunological reactions. These include identical twins having matching MHC/HLA types.

[0198] T cells can be “autologous” if the transferred cells are obtained from and transplanted to the same subject.

[0199] T cells can be “matched allogeneic” if the transferred cells are obtained from and transplanted to different members of the same species, yet have sufficiently matched major histocompatibility complex (MHC/HLA) antigens to avoid an adverse immunogenic response. Determining the degree of MHC/HLA mismatch may be accomplished according to standard tests known and used in the art (see, e.g., Mickelson and Petersdorf (1999) Hematopoietic Cell Transplantation, Thomas, E. D. et al. eds., pg 28-37, Blackwell Scientific, Malden, Mass; Vaughn, Method. Mol. Biol. MHC Protocol. 210:45-60 (2002); Morishima et al., Blood 99:4200-4206 (2002)).

[0200] T cells can be “mismatched allogeneic”, which refers to deriving from, originating in, or being members of the same species having non-identical MHC/HLA antigens (i.e., proteins) as typically determined by standard assays used in the art, such as serological or molecular analysis of a defined number of MHC/HLA antigens, sufficient to elicit adverse immunogenic responses. A “partial mismatch” refers to partial match of the MHC/HLA antigens tested between members, typically between a donor and recipient. For instance, a “half mismatch” (haplo -mismatch) refers to 50% of the MHC/HLA antigens tested as showing different MHC/HLA antigen type between two members. A “full” or “complete” mismatch refers to all MHC/HLA antigens tested as being different between two members.

[0201] T cells can be “xenogeneic”, which refers to deriving from, originating in, or being members of different species, e.g., human and rodent, human and swine, human and chimpanzee, etc. Further, T cells can be “transgenic”, e.g., engineered to express a T cell receptor specific for a stimulatory antigen, or to relieve checkpoint inhibition.

[0202] T cells can be obtained from a number of sources, including peripheral blood mononuclear cells (PBMCs), bone marrow, lymph node tissue, spleen tissue, thymic tissue, tumor issue, and umbilical cord. In certain embodiments, any number of T cell lines available in the art, may be used. In certain embodiments, T cells are obtained from a unit of blood collected from a subject using any number of techniques known to the skilled artisan, such as Ficoll separation. For example, cells from the circulating blood of a subject can be obtained by apheresis or leukapheresis. The apheresis product typically contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, red blood cells, and platelets. In some embodiments, the cells collected by apheresis can be washed to remove the plasma fraction and to place the cells in an appropriate buffer or medium for subsequent processing steps.

[0203] In another method, T cells are isolated from peripheral blood by lysing red blood cells and depleting monocytes, for example, by centrifugation through a PERCOLL™ gradient or adherence to plastic. Alternatively, T cells can be isolated from blood harvested from umbilical cord. Alternatively, T cells can be isolated from tumor tissue by enzymatic digestion and/or mechanical disruption.

[0204] A plurality of T cells of interest (e.g., T cells specific to an inhibitory antigen that dampens, imhibits or suppresses immune responses) can then be obtained or isolated (e.g., sorted) from an initial source, e.g., a sample of PBMCs. In one embodiment, fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS), is used to sort, analyze, and/or isolate T cells of interest. For example, cells having a cellular marker or other specific marker of interest can be tagged with an antibody, or a mixture of antibodies, that bind one or more of the cellular markers. Each antibody directed to a different marker can be conjugated to a detectable molecule, e.g., a fluorescent dye that may be distinguished from other fluorescent dyes coupled to other antibodies. A stream of tagged or “stained” cells can be passed through a light source that excites the fluorochrome and the emission spectrum from the cells detected to determine the presence of a particular labeled antibody. By concurrent detection of different fluorochromes (multicolor fluorescence cell sorting), cells displaying different sets of cell markers can be identified and isolated from other cells in the population. Other FACS and MACs parameters, including, e.g., side scatter (SSC), forward scatter (FSC), and vital dye staining (e.g., with propidium iodide) allow selection of cells based on size and viability. FACS and MACS sorting and analysis are well-known in the art and described in, for example, U.S. Pat. Nos. 5,137,809; 5,750,397; 5,840,580; 6,465,249; Miltenyi, et al., Cytometry 11:231-238 (1990). General guidance on fluorescence activated cell sorting is described in, for example, Shapiro (2003) Practical Flow Cytometry, 4th Ed., Wiley -Liss (2003) and Ormerod (2000) Flow Cytometry: A Practical Approach, 3rd Ed., Oxford University Press.

[0205] Another method of isolating T cells of interest involves a solid or insoluble substrate to which is bound antibodies or ligands that interact with specific cell surface markers. In immunoadsorption techniques, cells can be contacted with the substrate (e.g, column of beads, flasks, magnetic particles, etc.) containing the antibodies and any unbound cells removed.

Immunoadsorption techniques can be scaled up to deal directly with the large numbers of cells in a clinical harvest. Suitable substrates include, e.g, plastic, cellulose, dextran, polyacrylamide, agarose, and others known in the art (e.g., Pharmacia Sepharose 6 MB macrobeads). When a solid substrate comprising magnetic or paramagnetic beads is used, cells bound to the beads can be readily isolated by a magnetic separator (see, e.g., Kato et al., Cytometry 14:384-92 (1993)). Affinity chromatographic cell separations can involve passing a suspension of cells over a support bearing a selective ligand immobilized to its surface. The ligand interacts with its specific target molecule on the cell and is captured on the matrix. The bound cell is released by the addition of an elution agent to the running buffer of the column and the free cell is washed through the column and harvested as a homogeneous population. As apparent to the skilled artisan, adsorption techniques may use nonspecific adsorption.

[0206] FACS, MACS, and most batch-wise immunoadsorption techniques can be adapted to both positive and negative selection procedures (see, e.g., U.S. Pat. No. 5,877,299). In positive selection, the desired cells are labeled with antibodies and removed away from the remaining unlabeled/unwanted cells. In negative selection, the unwanted cells are labeled and removed.

Another type of negative selection that may be employed is use of antibody /complement treatment or immunotoxins to remove unwanted cells.

[0207] In some embodiments, a population of cells can be obtained (e.g. , using a sorting method described herein) and used in methods of the disclosure that comprises more than about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more (e.g., about 65% to about 90%, about 65% to about 95%, about 80% to about 90%, about 80% to about 95%, about 85% to about 90%, about 85% to about 95%, or about 90% to about 95%), cells of interest (e.g., T cells that mediate an immune response to at least one stimulatory antigen). In some embodiments, a population of cells (e.g., a depleted cell population described herein) can be obtained (e.g, using a sorting method described herein) and used in methods of the disclosure that comprises less than about 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or less (e.g., about 5% to about 10%, about 4% to about 10%, about 3% to about 10%, about 2% to about 10%, about 1% to about 10%, about 1% to about 5%, or about 2% to about 5%), or lack any detectable, cells of interest (e.g., T cells that mediate an immune response to at least one stimulatory antigen).

[0208] The obtained populations of cells can be used directly in a method of the disclosure, or can be frozen for use at a later date using a known method. For example, cells can be frozen using a freezing medium comprising 5-10% DMSO, 10-90% serum albumin, and 50-90% culture medium, or using a commercially available medium such as CS10 (STEMCELL Technologies). Other additives useful for preserving cells include, e.g., disaccharides such as trehalose (Scheinkonig et al., Bone Marrow Transplant. 34:531-536 (2004)), a plasma volume expander (such as hetastarch), and/or isotonic buffer solutions (such as phosphate-buffered saline). Compositions and methods for cryopreservation are well-known in the art (see, e.g, Broxmeyer et al., Proc. Natl. Acad. Sci. U.S.A. 100:645-650 (2003)).

[0209] Methods of stimulating and/or expanding antigen-specific T cells, and methods of non- specifically stimulating T cells, methods of expanding T cells, and methods of administering T cells are further described in WO 2021/203022, the contents of which are incorporated herein by reference in their entirety.

Methods of Identifying Immune Responses of a Subject

[0210] The disclosure provides methods of identifying one or more immune responses of a subject. In some embodiments, one or more immune responses of a subject are determined by a) providing a library described herein that includes a panel of antigens (e.g., autoantigens, tumor antigens, antigens identified from pathogens/infectious agents, tissue-specific or non-specific antigens, e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue, and/or other polypeptides of interest identified using a method described herein); b) contacting the library with antigen presenting cells from the subject; c) contacting the antigen presenting cells with lymphocytes from the subject; and d) determining whether one or more lymphocytes are stimulated by, inhibited and/or suppressed by, activated by, or non-responsive to one or more tumor antigens presented by one or more antigen presenting cells. In some embodiments, the library includes about 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, or more antigens.

[0211] In some embodiments, lymphocyte stimulation, non-stimulation, inhibition and/or suppression, activation, and/or non-responsiveness is determined by assessing levels of one or more expressed or secreted cytokines or other immune mediators described herein. In some embodiments, levels of one or more expressed or secreted cytokines that is at least 20%, 40%, 60%, 80%, 100%, 120%, 140%, 160%, 180%, 200% or more, higher than a control level indicates lymphocyte stimulation. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 standard deviations greater than the mean of a control level indicates lymphocyte stimulation. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 median absolute deviations (MADs) greater than a median response level to a control indicates lymphocyte stimulation. In some embodiments, a control is a negative control, for example, a clone expressing Neon Green (NG). In some embodiments, a level of one or more expressed or secreted cytokines that is at least 20%, 40%, 60%, 80%, 100%, 120%, 140%, 160%, 180%, 200% or more, lower than a control level indicates lymphocyte inhibition and/or suppression. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 standard deviations lower than the mean of a control level indicates lymphocyte inhibition and/or suppression. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 median absolute deviations (MADs) lower than a median response level to a control indicates lymphocyte inhibition and/or suppression. In some embodiments, a control is a negative control, for example, a clone expressing Neon Green (NG). In some embodiments, levels of one or more expressed or secreted cytokines that is at least 20%, 40%, 60%, 80%, 100%, 120%, 140%, 160%, 180%, 200% or more, higher or lower than a control level indicates lymphocyte activation. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 standard deviations greater or lower than the mean of a control level indicates lymphocyte activation. In some embodiments, a level of one or more expressed or secreted cytokines that is at least 1, 2, 3, 4 or 5 median absolute deviations (MADs) greater or lower than a median response level to a control indicates lymphocyte activation. In some embodiments, a control is a negative control, for example, a clone expressing Neon Green (NG). In some embodiments, a level of one or more expressed or secreted cytokines that is within about 20%, 15%, 10%, 5%, or less, of a control level indicates lymphocyte non-responsiveness or non-stimulation. In some embodiments, a level of one or more expressed or secreted cytokines that is less than 1 or 2 standard deviations higher or lower than the mean of a control level indicates lymphocyte non-responsiveness or nonstimulation. In some embodiments, a level of one or more expressed or secreted cytokines that is less than 1 or 2 median absolute deviations (MADs) higher or lower than a median response level to a control indicates lymphocyte non-responsiveness or non-stimulation. In some embodiments, a subject response profile can include a quantification, identification, and/or representation of a panel of different cytokines (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more cytokines) and of the total number of antigens (e.g., of all or a portion of different antigens from the library) that stimulate, do not stimulate, inhibit and/or suppress, activate, or have no or minimal effect on production, expression or secretion of each member of the panel of cytokines.

Methods of Selecting Antigens and Methods of Inducing or Inhibiting an Immune Response in a Subject

[0212] In general, immune responses can be usefully defined in terms of their integrated, functional end-effects. Dhabar et al. (2014) have proposed that immune responses can be categorized as being immunoprotective, immunopathological, and immunoregulatory. While these categories provide useful constructs with which to organize ideas, an overall in vivo immune response is likely to consist of several types of responses with varying amounts of dominance from each category.

[0213] Immunoprotective responses are defined as responses that promote efficient wound healing, eliminate infections and cancer, and mediate vaccine -induced immunological memory. These responses are associated with cytokines and mediators such as IFN-gamma, IL-12, IL-2, Granzyme B, CD 107, etc.

[0214] Immunopathological responses are defined as those that are directed against self (autoimmune disease like multiple sclerosis, arthritis, lupus) or innocuous antigens (asthma, allergies) and responses involving chronic, non-resolving inflammation. These responses can also be associated with molecules that are implicated in immunoprotective responses, but also include immune mediators such as TNF-alpha, IL-10, IL-13, IL-17, IL-4, IgE, histamine, etc. [0215] Immunoregulatory responses are defined as those that involve immune cells and factors that regulate (mostly down-regulate) the function of other immune cells. Recent studies suggest that there is an arm of the immune system that functions to inhibit immune responses. For example, regulatory CD4⁺CD25⁺FoxP3⁺T cells, IL-10, and TGF-beta, among others have been shown to have immunoregulatory/inhibitory functions. The physiological function of these factors is to keep pro-inflammatory, allergic, and autoimmune responses in check, but they may also suppress antitumor immunity and be indicative of negative prognosis for cancer. In the context of tumors, the expression of co-stimulatory molecules often decreases, and the expression of co-inhibitory ligands increases. MHC molecules are often down-regulated on tumor cells, favoring their escape. The tumor micro-environment, including stromal cells, tumor associated immune cells, and other cell types, produce many inhibitory factors, such as, IL-10, TGF-P, and IDO. Inhibitory immune cells, including T regs, Tri cells, immature DCs (iDCs), pDCs, and MDSC can be found in the tumor micro-environment. (Y Li UT GSBS Thesis 2016). Examples of mediators and their immune effects are shown in Table 2.

Table 2: Immune Mediators

ID = Infectious disease

IA = Autoimmune disease

[0216] The disclosure provides methods and systems for identifying and selecting (or deselecting) antigens (e.g., stimulatory and/or inhibitory antigens). In some embodiments, a stimulatory antigen is an antigen that stimulates one or more lymphocyte responses that are beneficial to a subject. In some embodiments, a stimulatory antigen is an antigen that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject. In some embodiments, a stimulatory antigen is an antigen that stimulates one or more lymphocyte responses that are harmful to a subject.

[0217] In other embodiments, in the context of autoimmune disease or overactive immune condition, a stimulatory antigen stimulates one or more lymphocyte responses that are deleterious or non-beneficial to a subject, and/or inhibits and/or suppresses one or more lymphocyte responses that are beneficial to a subject.

[0218] In some embodiments, an inhibitory antigen is an antigen that stimulates one or more lymphocyte responses that are deleterious or non-beneficial to a subject having an autoimmune disease or overactive immune condition. In some embodiments, an inhibitory antigen is an antigen that inhibits and/or suppresses one or more lymphocyte responses that are beneficial to the subject.

[0219] In other embodiments, in the context of autoimmune diseas or overactive immune condition e, an inhibitory antigen inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject, and/or stimulates one or more lymphocyte responses that are beneficial to a subject.

[0220] In some embodiments, an inhibitory antigen is an autoantigen that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject having an autoimmune disease or overactive immune condition. In some embodiments, an inhibitory antigen is an autoantigen that stimulates one or more lymphocyte responses that are beneficial to a subject having an autoimmune disease or overactive immune condition.

[0221] In some embodiments, an inhibitory antigen is a tumor antigen that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject having an autoimmune disease or overactive immune condition. In some embodiments, an inhibitory antigen is a tumor antigen that stimulates one or more lymphocyte responses that are beneficial to a subject having an autoimmune disease or overactive immune condition.

[0222] In some embodiments, an inhibitory antigen is an antigen identified from a pathogen/infectious agent that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to a subject having an autoimmune disease or overactive immune condition. In some embodiments, an inhibitory antigen is an antigen identified from a pathogen/infectious agent that stimulates one or more lymphocyte responses that are beneficial to a subject having an autoimmune disease or overactive immune condition.

[0223] In some embodiments, an inhibitory antigen is a tissue-specific antigen (e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue), that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non- beneficial to a subject having an autoimmune disease. In some embodiments, an inhibitory antigen is a tissue-specific antigen (e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue), that stimulates one or more lymphocyte responses that are beneficial to a subject having an autoimmune disease. [0224] In some embodiments, an inhibitory antigen is a tissue non-specific antigen (e.g.. identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue), that inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non- beneficial to a subject having an autoimmune disease. In some embodiments, an inhibitory antigen is a tissue non-specific antigen (e.g., identified from a cell or tissue that is a target of an autoimmune response, or from a healthy cell or tissue), that stimulates one or more lymphocyte responses that are beneficial to a subject having an autoimmune disease.

[0225] Additionally or alternatively, antigens may be identified and/or selected (or deselected) based on association with desirable or beneficial responses, e.g, clinical responses. Additionally or alternatively, antigens may be identified and/or selected (or de-selected) based on association with undesirable, deleterious or non-beneficial responses, e.g, clinical responses. Antigens may be identified and/or selected (or de-selected) based on a combination of the preceding methods, applied in any order.

[0226] Responses whereby antigens or immunogenic fragments thereof (i) stimulate lymphocyte responses that are beneficial to the subject, (ii) stimulate expression of cytokines that are beneficial to the subject, (iii) inhibit and/or suppress lymphocyte responses that are deleterious or non- beneficial to the subject, or (iv) inhibit and/or suppress expression of cytokines that are deleterious or non-beneficial to the subject, are termed “beneficial responses”.

[0227] In some embodiments, a selected antigen stimulates one or more lymphocyte responses that are beneficial to the subject. In some embodiments, a selected antigen inhibits and/or suppresses one or more lymphocyte responses that are deleterious or non-beneficial to the subject.

[0228] In some embodiments, a selected antigen increases expression and/or secretion of cytokines that are beneficial to the subject. In some embodiments, a selected antigen inhibits and/or suppresses expression of cytokines that are deleterious or non-beneficial to the subject.

[0229] In some embodiments, administration of one or more selected antigens to a subject suffering from an autoimmune disease or overactive immune condition inhibits and/or suppresses an immune response of the subject. In some embodiments, administration of one or more selected antigens to the subject elicits a beneficial immune response of the subject. In some embodiments, administration of one or more selected antigens to the subject elicits a beneficial response of the subject. In some embodiments, administration of one or more selected antigens to the subject improves clinical response of the subject to an immune therapy.

[0230] Responses whereby antigens or immunogenic fragments thereof (i) stimulate lymphocyte responses that are deleterious or not beneficial to the subject, (ii) stimulate expression of cytokines that are deleterious or not beneficial to the subject, (iii) inhibit and/or suppress lymphocyte responses that are beneficial to the subject, or (iv) inhibit and/or suppress expression of cytokines that are beneficial to the subject, are termed “deleterious or non-beneficial responses”.

[0231] In some embodiments, one or more antigens are selected (or de-selected) based on association with desirable or beneficial immune responses. In some embodiments, one or more antigens are selected (or de-selected) based on association with undesirable, deleterious, or non- beneficial immune responses.

[0232] In some embodiments, a selected antigen stimulates one or more lymphocyte responses that are deleterious or non-beneficial to the subject. In some embodiments, a selected antigen inhibits and/or suppresses one or more lymphocyte responses that are beneficial to the subject.

[0233] In some embodiments, a selected antigen increases expression and/or secretion of cytokines that are deleterious or non-beneficial to the subject. In some embodiments, a selected antigen inhibits and/or suppresses expression of cytokines that are beneficial to the subject.

[0234] In some embodiments, one or more antigens are de-selected by the methods herein. In some embodiments, one or more selected antigens are excluded from administration to a subject.

[0235] In some embodiments, selected inhibitory antigens comprise an antigen described herein (e.g., comprising an amino acid sequence described herein). In some embodiments, selected inhibitory antigens comprise a polypeptide having an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence of an antigen described herein. In some embodiments, selected inhibitory antigens comprise a polypeptide comprising the amino acid sequence of an antigen described herein having at least one deletion, insertion, and/or translocation.

Methods of Measuring a Lymphocyte Response

[0236] The response of a lymphocyte may be determined, e.g., by measuring the level/expression of certain immune mediators, or by measuring the pathology of a tissue in a subject.

[0237] In some embodiments, lymphocyte response may be measured at a cellular level. In some embodiments, lymphocyte response may be measured by performing assays to measure the level of certain immune mediators. Assays may include, but are not limited to the antigen presentation assays described previously. Immune mediators measured may be known immune mediators and immune mediators described herein, for example, cytokines. An exemplary assay to measure lymphocyte response may be an assay that uses an enzyme-linked immunosorbent assay (ELISA) technique, such as an ELISpot assay. Assays may also include analysis of upregulation of cell surface molecules such as co-stimulatory molecules (i.e., CD28, LFA-1, CD137 [4-1BB], CD154 [CD40L]), effector memory markers (i.e. CD45RO, CD62L), or HLA molecules by flow cytometry.

Assays may also include evaluation of beneficial genes via gene chip analyses.

[0238] At a cellular level, immune responses of lymphocytes may be determined by the percent change in cytokine secretion in response to an identified antigen compared to a control level where the antigen is not presented for example, by more than 5%, 6%, 7%, 8%, 9%, 10%, or 20%. A control level may be without presentation of an antigen or without the addition of a composition to induce redirection of an immune response or re-education, such as an adjuvant. Redirection of an immune response or re-education may be determined by a change in levels of immune mediators in response to an antigen presented alone compared to an antigen presented in combination with an adjuvant. Redirection of an immune response or re-education may be determined by a change in levels of one or more immune mediators over time, for example, by more than 5%, 6%, 7%, 8%, 9%, 10%, or 20%. In some embodiments, redirection of an immune response or re-education may be determined by a change in the levels of different immune mediators produced by a lymphocyte, or the change in the predominant type of immune mediator produced by a lymphocyte in response to the presentation of an antigen. For example, the change in expression and/or secretion of IL-10 to IFN- gamma may indicate redirection or re-education from an immunosuppressive response to an immunostimulatory response.

[0239] At the tissue level, an immune response may be measured by the pathology of a tissue in a subject. In some embodiments, infiltration of tissues with immune cells can be monitored with multi-parameter immuunohistochemistry, T cell receptor sequencing, or evaluation of enriched tumor infiltrating lymphocytes using conventional immunoassays. Redirection of immune response or reeducation of lymphocytes can be determined by an increase in tumor infiltration by T cells.

[0240] Stimulation, or conversely inhibition or suppression, of immune responses or of lymphocytes at a tissue or systemic level may be determined by evaluation of the diversity, clonality, persistence, and other features of the T cell receptor (TCR) repertoire via TCR sequencing.

[0241] T cell receptors (“TCRs”) are complexes of several polypeptides that are able to bind an antigen when expressed on the surface of a cell, such as a T lymphocyte. The a and (3 chains, or subunits, form a dimer that is independently capable of antigen binding. The a and (3 subunits typically comprise a constant domain and a variable domain.

[0242] A T cell receptor includes a complex of polypeptides comprising a T cell receptor a subunit and a T cell receptor (3 subunit. The a and (3 subunits may be native, full-length polypeptides, or may be modified in some way, provided that the T cell receptor retains the ability to bind antigen. For example, the a and (3 subunits may be amino acid sequence variants, including substitution, addition and deletion mutants. They may also be chimeric subunits that comprise, for example, the variable regions from one organism and the constant regions from a different organism. [0243] T cells play the role of central organizer of the immune response by recognizing antigens through T cell receptors (TCR). The specificity of a T cell depends on the sequence of its T cell receptor. The genetic template for this receptor is created during T cell development in the thymus by the V(D)J DNA rearrangement process, which imparts a unique antigen specificity upon each TCR. The TCR plays an essential role in T cell function, development and survival.

[0244] In some embodiments, T cells derived from non-specific, heterogeneous populations can be converted into T cells capable of responding to protein antigens and tumor tissues. In some embodiments, an antigen-specific T cell is characterized by the ability of the TCR of a T cell to recognize at least one antigen (e.g., a tumor antigen). Antigen-specific T cells can include e.g., cytotoxic T cells, assisted T cells, natural killer T cells, gamma delta T cells, regulatory T cells and memory T cells or more, but may be preferably memory T cells.

[0245] In some embodiments, after successful stimulation of immune responses or of lymphocytes, the diversity of the TCR repertoire or the clonality of the TCR repertoire may increase. In other cases, the persistence of a TCR clonotype may indicate T cell engraftment and establishment of a long-term immune response.

Immunogenic Compositions and Uses Thereof

[0246] The present disclosure provides compositions that include an antigen or antigens described herein and/or identified or selected by methods described herein, nucleic acids encoding the antigens, and methods of using the compositions. In some embodiments, antigens of the compositions include one or more inhibitory antigens. In some embodiments, antigens of the compositions include both inhibitory antigens and stimulatory antigens. In some embodiments, a composition includes antigens that are peptides 8-40 amino acids, 8-60 amino acids, 8-100 amino acids, 8-150 amino acids, or 8-200 amino acids in length (e.g., MHC binding peptides, e.g., peptides 23-29, 24-28, 25-27, 8-30, 8-29, 8-28, 8-27, 8-26, 8-25, 8-24, 8-23, 8-22, 8-21, 8-20, 8-15, or 8-12 amino acids in length). In some embodiments, a composition includes one or more antigens that are about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of the length of the full-length polypeptides. In some embodiments, a composition includes one or more antigens that are truncated by about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or more amino acids, relative to the full-length polypeptides. The compositions can include antigens that are, or that comprise, MHC class I-binding peptides, MHC class Il-binding peptides, or both MHC class I and MHC class Il-binding peptides. Compositions can include a single antigen, or multiple antigens. In some embodiments, a composition includes a set of two, three, four, five, six, seven, eight, nine, ten, or more antigens. In some embodiments, a composition includes ten, fifteen, twenty, twenty -five, thirty, or more antigens. In some embodiments, the antigens or peptides are provided as one or more fusion proteins. In some embodiments, a composition comprises nucleic acids encoding the antigens or peptides. In some embodiments, the nucleic acids encoding the antigens or peptides are provided as one or more fusion constructs.

[0247] The disclosure also provides nucleic acids encoding the antigens. The nucleic acids can be used to produce expression vectors, e.g., for recombinant production of antigens, or for nucleic acid-based administration in vivo (e.g., DNA vaccination). In some embodiments, the nucleic acid is a DNA or an RNA. In some embodiments, the RNA is an mRNA.

[0248] In some embodiments, antigens are used in diagnostic assays. For these assays, compositions including the antigens can be provided in kits, e.g, for detecting antibody reactivity, or cellular reactivity, in a sample from an individual.

[0249] In some embodiments, antigen compositions are used to induce an immune response in a subject. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The antigen compositions can be used to raise antibodies (e.g., in a non-human animal, such as a mouse, rat, hamster, or goat), e.g, for use in diagnostic assays, and for therapeutic applications. In some embodiments, an antigen discovered by a method described herein may be a potent B cell antigen. Preparations of antibodies may be produced by immunizing a subject with the antigen and isolating antiserum from the subject. Methods for eliciting high titers of high affinity, antigen-specific antibodies, and for isolating the antigen-specific antibodies from antisera, are known in the art. In some embodiments, the antigen compositions are used to raise monoclonal antibodies, e.g, human monoclonal antibodies. In some embodiments, the antigen compositions may induce a T cell response. In some embodiments, the antigen compositions may induce a T cell response and a B cell response.

[0250] In some embodiments, an antigen composition is used to induce an immune response in a human subject to provide a therapeutic response. In some embodiments, an antigen composition is used to induce an immune response in a human subject that redirects an undesirable immune response. In some embodiments, an antigen composition elicits an immune response that causes the subject to have a positive clinical response described herein, e.g., as compared to a subject who has not been administered the antigen composition. In some embodiments, an antigen composition elicits an immune response that causes the subject to have an improved clinical response, e.g., as compared to a subject who has not been administered the antigen composition. In some embodiments, an antigen composition is used to induce an immune response in a human subject for palliative effect. The immune response can result in complete or partial therapy.

[0251] In some embodiments, an antigen composition is used to induce an immune response in a human subject to provide a prophylactic response. The immune response can result in complete or partial protection. [0252] In some embodiments, the composition includes a pharmaceutically acceptable carrier or excipient in order to alter, redirect, or re-educate the immune response of a subject or a lymphocyte.

[0253] The disclosure also provides a vaccine for inhibiting or decreasing an immune response in a subject with an autoimmune disease comprising an inhibigen and an effective amount of an adjuvant. In some embodiments, the vaccine comprises inhibigen comprises one or more antigens of the disclosure. In some embodiments, the the inhibigen is a peptide. In some embodiments, the peptide is encoded by a nucleic acid. In some embodiments, the nucleic acid is a vector. In some embodiments, the nucleic acid is a DNA or a RNA. In some embodiments, the nucleic acid is an RNA, optionally wherein the RNA is an mRNA. In some embodiments, the inhibigen is obtained by a method comprising: a) providing a plurality of bacterial cells or beads, wherein each bacterial cell or bead comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with human antigen presenting cells (APCs); c) contacting the APCs with a plurality of human lymphocytes; e) identifying one or more polypeptides that inhibit and/or suppress cytolytic T cell activity; and 1) selecting one or more inhibitory polypeptides; thereby selecting the inhibigen. In some embodiments, the method further comprises contacting the APCs with an adjuvant.

[0254]

Adjuvants

[0255] An immunogenic composition may also include an adjuvant for enhancing the immunogenicity of the formulation, (e.g., oil in water, incomplete Freund's adjuvant, aluminum phosphate, aluminum hydroxide, saponin adjuvants, toll-like receptor agonists, or muramyl dipeptides).

[0256] Adjuvants can be broadly separated into two classes, based on their principal mechanisms of action: vaccine delivery systems and immunostimulatory adjuvants (see, e.g., Singh et al., Curr. HIV Res. 1:309-20, 2003). Vaccine delivery systems are often particulate formulations, e.g, emulsions, microparticles, immune -stimulating complexes (ISCOMs), which may be, for example, particles and/or matrices, and liposomes. In contrast, immuno stimulatory adjuvants are sometimes derived from pathogens and can represent pathogen associated molecular patterns (PAMP), e.g, lipopolysaccharides (LPS), monophosphoryl lipid (MPL), or CpG-containing DNA, which activate cells of the innate immune system.

[0257] Alternatively, adjuvants may be classified as organic and inorganic. Inorganic adjuvants include alum salts such as aluminum phosphate, amorphous aluminum hydroxyphosphate sulfate, and aluminum hydroxide, which are commonly used in human vaccines. Organic adjuvants comprise organic molecules including macromolecules. An example of an organic adjuvant is cholera toxin.

[0258] Adjuvants may also be classified by the response they induce, and adjuvants can activate more than one type of response. In some embodiments, the adjuvant induces the activation of CD4⁺ T cells. The adjuvant may induce activation of TH1 cells and/or activation of TH17 cells and/or activation of TH2 cells. Alternately, the adjuvant may induce activation of TH1 cells and/or TH 17 cells but not activation of TH2 cells, or vice versa. In some embodiments, the adjuvant induces activation of CD8⁺ T cells. In further embodiments, the adjuvant may induce activation of Natural Killer T (NKT) cells. In some embodiments, the adjuvant induces the activation of TH1 cells or TH17 cells or TH2 cells. In other embodiments, the adjuvant induces the activation of B cells. In yet other embodiments, the adjuvant induces the activation of antigen-presenting cells. These categories are not mutually exclusive; in some cases, an adjuvant activates more than one type of cell.

[0259] In certain embodiments, an adjuvant is a substance that increases the numbers or activity of antigen presenting cells such as dendritic cells. In certain embodiments, an adjuvant promotes the maturation of antigen presenting cells such as dendritic cells. In some embodiments, an adjuvant is an inflammasome activator. In some embodiments the inflammasome activator is aluminum potassium sulfate, a RIG-I agonist such as Poly(dA:dT), a TLR5 agonist such as flagellin, or a dectin- 1 antagonist such as Curdlan. In some embodiments, the adjuvant is or comprises a saponin. Typically, the saponin is a triterpene glycoside, such as those isolated from the bark of the Quillaja saponaria tree. A saponin extract from a biological source can be further fractionated (e.g., by chromatography) to isolate the portions of the extract with the best adjuvant activity and with acceptable toxicity. Typical fractions of extract from Quillaja saponaria tree used as adjuvants are known as fractions A and C. An exemplary saponin adjuvant is QS-21, which is available from Antigenics. QS-21 is an oligosaccharide-conjugated small molecule. Optionally, QS-21 may be admixed with a lipid such as 3D-MPL or cholesterol.

[0260] A particular form of saponins that may be used in vaccine formulations described herein is immunostimulating complexes (ISCOMs). ISCOMs are an art-recognized class of adjuvants that generally comprise Quillaja saponin fractions and lipids (e.g., cholesterol and phospholipids such as phosphatidyl choline). In certain embodiments, an ISCOM is assembled together with a polypeptide or nucleic acid of interest. However, different saponin fractions may be used in different ratios. In addition, the different saponin fractions may either exist together in the same particles or have substantially only one fraction per particle (such that the indicated ratio of fractions A and C are generated by mixing together particles with the different fractions). In this context, "substantially" refers to less than 20%, 15%, 10%, 5%, 4%, 3%, 2% or even 1%. Such adjuvants may comprise fraction A and fraction C mixed into a ratio of 70-95 A: 30-5 C, such as 70 A : 30 C to 75 A : 25 C, 75 A : 25 C to 80 A : 20 C, 80 A : 20 C to 85 A : 15 C, 85 A : 15 C to 90 A : 10 C, 90 A : 10 C to 95 A : 5 C, or 95 A : 5 C to 99 A : 1 C. ISCOMatrix, produced by CSL, and AblSCO 100 and 300, produced by Isconova, are ISCOM matrices comprising saponin, cholesterol and phospholipid (lipids from cell membranes), which form cage-like structures typically 40-50 nm in diameter. Posintro, produced by Nordic Vaccines, is an ISCOM matrix where the immunogen is bound to the particle by a multitude of different mechanisms, e.g. electrostatic interaction by charge modification, incorporation of chelating groups or direct binding.

[0261] In some embodiments, the adjuvant is a TLR agonist, a STING agonist, or a molecule that triggers the inflammasome. In some embodiments, the TLR agonist is a TLR2 agonist such as Pam3CSK4. In some embodiments, the TLR agonist is a TLR3 agonist such as Poly-IC or Poly- ICLC (Hiltonol). In some embodiments, the TLR agonist is a TLR4 agonist such as 3D-PHAD. In some embodiemnts the TLR agonist is a TLR7 agonist such as imiquimod or R848. In some embodiments, the TLR agonist is a TLR5 agonist such as flagellin. In some embodiments, the TLR agonist is a TLR9 agonist such as CpG.

[0262] In some embodiments, the adjuvant is a nanoemulsion that is a high-energy, oil-in- water emulsion with a size of 150-400 nanometers, and includes surfactants to provide stability.

[0263] Adjuvants may be covalently bound to antigens (e.g., the polypeptides described above). In some embodiments, the adjuvant may be a protein which induces inflammatory responses through activation of antigen-presenting cells (APCs). In some embodiments, one or more of these proteins can be recombinantly fused with an antigen of choice, such that the resultant fusion molecule promotes dendritic cell maturation, activates dendritic cells to produce cytokines and chemokines, and ultimately, enhances presentation of the antigen to T cells and initiation of T cell responses (see Wu et al., Cancer Res 2005; 65(11), pp 4947-4954). Other exemplary adjuvants that may be covalently bound to antigens comprise polysaccharides, small molecules, synthetic peptides, lipopeptides, and nucleic acids.

[0264] The adjuvant can be used alone or in combination of two or more kinds. Adjuvants may be directly conjugated to antigens. Adjuvants may also be combined to increase the magnitude of the immune response to the antigen. Typically, the same adjuvant or mixture of adjuvants is administered ateach stimulation event (e.g., vaccination, prime injection, or boost injection). Optionally, however, an adjuvant may be administered at the first stimulation but not subsequent stimulations. Alternatively, a strong adjuvant may be administered at initial stimulation, and a weaker adjuvant or lower dose of the strong adjuvant may be administered at subsequent re=stimulations. The adjuvant can be administered before the antigen, concurrent with the antigen or after administration of the antigen to a subject (sometimes within 1, 2, 6, or 12 hours; sometimes within 1, 2, or 5 days; sometimes within 1, 2, or 3 months; sometimes within 6, 12, or 18 months; sometimes within 2, 3, 4, 5, 10, or 15 years). In some embodiments, an adjuvant may be directly combined or formulated with an antigen to make a vaccine composition. In certain embodiments, an adjuvant may be administered separately from an antigen. An adjuvant may be administered separately but concurrently with an antigen, or may be administered separately in between doses of an antigen.

[0265] In some embodiments, immunogenicity of an antigen is evaluated in vivo. In some embodiments, humoral responses to an antigen are evaluated (e.g. , by detecting antibody titers to the administered antigen). In some embodiments, cellular immune responses to an antigen are evaluated, e.g, by detecting the frequency of antigen-specific cells in a sample from the subject (e.g., by staining T cells from the subject with MHC/peptide tetramers containing the antigenic peptide, to detect antigen-specific T cells, or by detecting antigen-specific cells using an antigen presentation assay such as an assay described herein). In some embodiments, the ability of an antigen or antigens to elicit protective or therapeutic immunity is evaluated in an animal model. In some embodiments, the ability of an antigen or antigens to stimulate or to suppress and/or inhibit immunity is evaluated in an animal model.

Carriers and Formulations

[0266] In some embodiments, an immunogenic composition includes an antigen linked to a carrier protein. Examples of carrier proteins include, e.g., toxins and toxoids (chemical or genetic), which may or may not be mutant, such as anthrax toxin, PA and DNI (PharmAthene, Inc.), diphtheria toxoid (Massachusetts State Biological Labs; Serum Institute of India, Ltd.) or CRM 197, tetanus toxin, tetanus toxoid (Massachusetts State Biological Labs; Serum Institute of India, Ltd.), tetanus toxin fragment Z, exotoxin A or mutants of exotoxin A of Pseudomonas aeruginosa, bacterial flagellin, pneumolysin, an outer membrane protein of Neisseria meningitidis (strain available from the ATCC (American Type Culture Collection, Manassas, Va.)), Pseudomonas aeruginosa Hcpl protein, E. coli heat labile enterotoxin, shiga-like toxin, human LTB protein, a protein extract from whole bacterial cells, and any other protein that can be cross-linked by a linker. Other useful carrier proteins include high density lipoprotein (HDL), bovine serum albumin (BSA), P40, and chicken riboflavin. Many carrier proteins are commercially available (e.g., from Sigma Aldrich).

[0267] In some embodiments, an immunogenic composition including anantigen identified by a method described herein is used in conjunction with an available vaccine. For example, an antigen identified as described herein can be used as a supplemental component of a vaccine formulation, or as a boosting antigen in a vaccination protocol.

[0268] In some embodiments, the nucleic acid encoding for one or more antigens or inhibigens is provided within a plasmid, a nanoplasmid, a phagemid, a phage derivative, a virus, a bacmid, a bacterial artificial chromosome (BAC), minicircle, doggybone, a yeast artificial chromosome (YAC), or a cosmid. [0269] In some embodiments, the virus is an alphavirus, a parvovirus, an adenovirus, an AAV, a baculovirus, a Dengue virus, a lentivirus, a herpesvirus, a poxvirus, an anellovirus, a bocavirus, a vaccinia virus, or a retrovirus.

[0270] In some embodiments, the AAV is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, AAV16, AAV-rh8, AAV-rhlO, AAV-rh20, AAV-rh39, AAV-rh74, AAV-rhM4-l, AAV-hu37, AAV-Anc80, AAV- Anc80L65, AAV-7m8, AAV-PHP-B, AAV-PHP-EB, AAV-2.5, AAV-2tYF, AAV-3B, AAV-LK03, AAV-HSC1, AAV-HSC2, AAV-HSC3, AAV-HSC4, AAV-HSC5, AAV-HSC6, AAV-HSC7, AAV- HSC8, AAV-HSC9, AAV-HSC10, AAV-HSC11, AAV-HSC12, AAV-HSC13, AAV-HSC14, AAV- HSC15, AAV-TT, AAV-DJ/8, AAV-Myo, AAV-NP40, AAV-NP59, AAV-NP22, AAV-NP66, or AAV-HSC16, or a derivative thereof.

[0271] In some embodiments, the herpesvirus is HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV- 7, or HHV-8.

[0272] In some embodiments, the nucleic acid encoding for one or more antigens or inhibigens is comprised in a non-viral delivery system. In some embodiments, the nucleic acid is comprised in a liposome. In some embodiments, the nucleic acid is associated with a lipid. The nucleic acid associated with a lipid, in some embodiments, is encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the nucleic acid, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, the nucleic acid is comprised in a lipid nanoparticle (LNP).

[0273] In some embodiments, an immunogenic composition is in a volume of about 0.5 mL for subcutaneous injection, 0.1 mL for intradermal injection, or 0.002-0.02 mL for percutaneous administration. A 0.5 ml dose of the composition may contain approximately 2-500 pg of the antigen.

Administration

[0274] In some embodiments an immunogenic composition is administered parenterally (for instance, by subcutaneous, intramuscular, intravenous, or intradermal injection). In some embodiments, delivery by a means that physically penetrates the dermal layer is used (e.g., a needle, airgun, or abrasion).

[0275] In some embodiments, an immunogenic composition is administered to a subject, e.g., by intramuscular injection, intradermal injection, or transcutaneous immunization with appropriate immune adjuvants. Compositions can be administered, one or more times, often including a second administration designed to boost an immune response in a subject. The frequency and quantity of dosage of the composition can vary depending on the specific activity of the composition and clinical response of the subject, and can be determined by routine experimentation.

[0276] The formulations of immunogenic compositions can be provided in unit-dose or multi-dose containers, for example, sealed ampoules and vials and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier immediately prior to use.

[0277] In some embodiments, the vaccine is administered using a virus, by electroporation, or in a liposome.

Combination Therapy

[0278] In some embodiments, compositions comprising an inhibitory antigen described herein can be administered in combination with another therapy, e.g., another therapy for an autoimmune disease or overactive immune condition.

[0279] The present disclosure is not limited to any specific therapy for an autoimmune disease or overactive immune condition, and any known or developed immune therapy is encompassed by the present disclosure.

[0280] In some embodiments, compositions comprising one or more identified inhibitory antigens can be administered in combination with an agent for treating an arthritic inflammatory condition. Examples of therapeutic agents commonly used for treating an arthritic inflammatory condition include the following: corticoids (prednisone), TNF blocking agents such as Infliximab, Adalimumab, Etanercept; - anti-interleukins such as Anakinra, AMG1 08, Iguratimod, Actemra, anti- B lymphocytes such as Rituximab, Epratuzumab; anti- costimulatory molecules such as Abatacept, Belimumab; tolerogenic agents (synthetic molecules directed to B lymphocyte surface DNA receptors) such as LJP 394 or TV-4710; - anti-complement protein such as Eculizumab; Inhibitors of T cell signalling molecules such as CP690550; Inhibitors of cell migration such as antagonist of chemokine receptors (Maraviroc, INCB3284) leflunomide, sulfasalazine, hydroxychloroquine, azathioprine, methotrexate, cyclosporine, minocycline, D-penicillamine, combination therapy thereof such as methotrexate + sulfasaline, methotrexate + hydroxychloroquine, methotrexate + azathioprine, methotrexate + infliximab, methotrexate + leflunomide, methotrexate + etanercept, cyclosporine + hydroxychloroquine, cyclosporine + methotrexate, methotrexate + sulfasalazine + hydroxychloroquine.

[0281] In some embodiments, compositions comprising one or more identified inhibitory antigens can be administered in combination with an agent for treating multiple sclerosis. Examples of therapeutic agents commonly used for treating multiple sclerosis include the following: one or more therapeutic agents in the group of interferon-beta, glatiramer acetate, mitoxantrone, cyclophosphamide, methotrexate, aziathropine and/or natalizumab.

[0282] In some embodiments, compositions comprising one or more identified inhibitory antigens (inhibigen) can be administered in combination with an agent for treating an intestinal inflammatory condition. Examples of therapeutic agents commonly used for treating an intestinal inflammatory condition include anti-TNF or TNF blocking agents, natalizumab, anti-ILl, anti-IL-6, anti- IL- 12, anti-IL-17 and anti-IL-23; IL-I receptor antagonist analogs (anakinra); 5 aminosalicyclic acid and analogs such as mesalazine, sulfazaline, olsalazine, balsalazide; corticoids such as prednisone, budesonide, hydrocortisone, prednisolone, methylprednisolone, betamethasone, bedomethasone, and/or tixocorto.

[0283] In some embodiments, compositions comprising one or more identified inhibitory antigens can be administered in combination with an agent for treating vasculitis (e.g., such as atherosclerosis and Wegener's disease). Examples of therapeutic agents commonly used for treating vasculitis include statins, aspirin, blood coagulants such as heparin, Coumadin for atherosclerosis and corticoids, aziathioprine, methothrexate, cyclophosphamide, anti-B lymphocytes antibodies (Rituximab) TNF blocking agents (Etanercept, Remicade) and/or anti-thymocyte globulin for Wegener's disease,

[0284] Therapeutic agents commonly used for treating inflammation related to transplant rejection (host versus graft disease or graft versus host disease) are calcineurins inhibitors (Cyclosporin, Tacrolimus), mTOR inhibitors (Sirolimus, Everolimus), anti -proliferative agents (Azathioprine, Mycophenolic acid), monoclonal antibodies directed to CD25 (Dacluzimab, Basiliximab) or anti-thymocyte and anti-lymphocyte globulin preparations.

[0285] Therapeutic agents commonly used for treating asthma are short-acting, selective be ta2 -adrenoceptor agonists, such as salbutamol (albuterol USAN), levalbuterol, terbutaline and bitolterol and other adrenergic agonists such as inhaled epinephrine and ephedrine tablets, anticholinergic medications such as ipratropium bromide, inhaled glucocorticoids.

[0286] Methods described herein can include preparing and/or providing a report, such as in electronic, web-based, or paper form. The report can include one or more outputs from a method described herein, e.g., a subject response described herein. In some embodiments, a report is generated, such as in paper or electronic form, which identifies the presence or absence of one or more antigens (e.g., one or more stimulatory and/or inhibitory antigens) for a patient, and optionally, a recommended course of therapy. In some embodiments, the report includes an identifier for the patient. In one embodiment, the report is in web-based form. [0287] In some embodiments, additionally or alternatively, a report includes information on prognosis, resistance to, or potential or suggested therapeutic options. The report can include information on the likely effectiveness of a therapeutic option, the acceptability of a therapeutic option, or the advisability of applying the therapeutic option to a patient, e.g., identified in the report. For example, the report can include information, or a recommendation, on the administration of a therapy, e.g, the administration of a pre-selected dosage or in a pre-selected treatment regimen, e.g, in combination with one or more alternative therapies, to the patient. The report can be delivered, e.g., to an entity described herein, within 7, 14, 21, 30, or 45 days from performing a method described herein. In some embodiments, the report is a personalized treatment report.

[0288] In some embodiments, a report is generated to memorialize each time a subject is tested using a method described herein. The subject can be reevaluated at intervals, such as every month, every two months, every six months or every year, or more or less frequently, to monitor the subject for responsiveness to a therapy and/or for an improvement in one or more symptoms, e.g, described herein. In some embodiments, the report can record at least the treatment history of the subject.

[0289] In one embodiment, the method further includes providing a report to another party. The other party can be, for example, the subject, a caregiver, a physician, an oncologist, a hospital, clinic, third-party payor, insurance company or a government office.

Production of Antigens

[0290] An antigen (e.g., an antigen described herein) or inhibigen suitable for use in any method or composition of the disclosure may be produced by any available means, such as recombinantly or synthetically (see, e.g., Jaradat Amino Acids 50:39-68 (2018); Behrendt et al., J. Pept. Sci. 22:4-27 (2016)). For example, an antigen may be recombinantly produced by utilizing a host cell system engineered to express an antigen-encoding nucleic acid. Alternatively or additionally, an antigen may be produced by activating endogenous genes.

[0291] Where proteins are recombinantly produced, any expression system can be used. To give but a few examples, known expression systems include, for example, E. coll, egg, baculovirus, plant, yeast, or mammalian cells.

[0292] In some embodiments, recombinant antigens or inhibigen suitable for the present disclosure are produced in mammalian cells. Non-limiting examples of mammalian cells that may be used in accordance with the present disclosure include BALB/c mouse myeloma line (NSO/1, EC ACC No: 85110503); human retinoblasts (PER.C6, CruCell, Leiden, The Netherlands); monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (HEK293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol., 36:59,1977); human fibrosarcoma cell line (e.g., HT1080); baby hamster kidney cells (BHK21, ATCC CCL 10); Chinese hamster ovary cells +/-DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad. Sci. USA, 77:4216, 1980); mouse sertoli cells (TM4, Mather, Biol. Reprod., 23:243-251, 1980); monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1 587); human cervical carcinoma cells (HeLa, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); mouse mammary tumor (MMT 060562, ATCC CCL51); TRI cells (Mather et al., Annals N.Y. Acad. Sci., 383:44-68, 1982); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2).

[0293] In some embodiments, the present disclosure provides recombinant antigens produced from human cells. In some embodiments, the present disclosure provides recombinant antigens produced from CHO cells or HT1080 cells.

[0294] Typically, cells that are engineered to express a recombinant antigen may comprise a transgene that encodes a recombinant antigen described herein. It should be appreciated that the nucleic acids encoding a recombinant antigen may contain regulatory sequences, gene control sequences, promoters, non-coding sequences and/or other appropriate sequences for expressing the recombinant antigen. Typically, the coding region is operably linked with one or more of these nucleic acid components.

[0295] The coding region of a transgene may include one or more silent mutations to optimize codon usage for a particular cell type. For example, the codons of an antigen transgene may be optimized for expression in a vertebrate cell. In some embodiments, the codons of an antigen transgene may be optimized for expression in a mammalian cell. In some embodiments, the codons of an antigen transgene may be optimized for expression in a human cell.

[0296] Alternatively or additionally, an antigen or inhibigen may be partially or fully prepared by chemical synthesis. These methods may include chemical synthesis such as solid phase and/or solution phase polypeptide synthesis. See for example, the methodology as described in Bruckdorfer, T. et al. (Curr. Pharm. Biotechnol. 5, 29-43 (2004)).

[0297] Alternatively or additionally, an antigen or inhibigen may be provided as a nucleic acid. In some embodiments, the nucleic acid is a DNA or a RNA.

[0298] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described herein.

[0299] The disclosure is further illustrated by the following examples. The examples are provided for illustrative purposes only. They are not to be construed as limiting the scope or content of the disclosure in any way.

EXAMPLES

[0300] Methods for identifying antigens that stimulate and/or inhibit (for example inhibit) the immune response are detailed below. In addition to identification of stimulatory or inhibitory antigens, methods of stimulating, dampening/decreasing and redirecting immune responses and/or reeducating T cells by administration of one or more adjuvants or other immune modulating agents are also demonstrated.

[0301] In certain examples, a melanoma model was employed to identify murine stimulatory and inhibitory antigens using ATLAS. Mice were implanted subcutaneously with B16F10 tumors, which were subsequently resected for whole exome sequencing and assessed for non-synonymous mutations. ATLAS libraries individually expressing each mutation were constructed and used to screen splenic T cells from tumor-bearing mice to identify stimulatory or inhibitory antigens. In subsequent experiments, candidate antigens were manufactured as synthetic long peptides and delivered subcutaneously to C57BL/6 mice with or without adjuvant to elucidate the ability of vaccines comprising stimulatory or inhibitory antigens to impact tumor growth.

Example 1. Identification of stimulatory and inhibitory antigens using mATLAS screens

Methods

[0302] A cohort of C57BL/6J mice bearing B16F10 tumors were euthanized and their tumors and spleens harvested. DNA obtained from pooled tumors was sequenced and analyzed for non- synonymous mutations. Over 1600 such mutations were identified, and these were synthesized as 399bp DNA fragments centered upon the base pair change and transformed individually into E. coli bacteria expressing cLLO to build a candidate neoantigen library. Splenocytes frozen from pooled spleens of the tumor-bearing mice were thawed, and CD8⁺ T cells were sorted using a negative selection bead kit. These were subsequently expanded with CD3/CD28 beads and IL-2 for 7 days followed by 1 day of rest after removal of beads and cytokine. Mouse APCs (RAW309 Cr.l macrophage cell line) were cultured overnight, washed with PBS, then co-cultured with the bacterial library for 2 hours, washed with PBS, and then cultured with the non-specifically expanded and rested CD8⁺ T cells overnight. Harvested supernatant from the co-culture was tested for IFNy and TNFa by a custom mouse 384-well Meso Scale Discovery (MSD) electrochemiluminescence assay.

Results

[0303] Sixty -eight antigens were identified as stimulatory (exceeding a statistical threshold above the negative control, a 399bp fragment of the mouse actin gene) and 57 antigens were identified as inhibitory (reduced beyond a statistical threshold below the negative control), for either IFNy, TNFa, or both (FIG. 1). Only 2% (6 of 283) of NetMHCpan (Nielsen et al., PLoS One. 2007 Aug 29;2(8):e796) predicted binding antigens were empirically identified by mATLAS as stimulatory antigens. 6% (17 of 283) of NetMHCpan predicted antigens were identified by mATLAS as inhibitory antigens (FIG. 2).

[0304] The top 50 stimulatory and 50 inhibitory antigens, and approximately 50 antigens closest to the negative control (non-responses), were used in two additional repeat mATLAS screens with increased replicates. Each antigen was ranked by its IFNy signal across all 3 screens, as well as a separate rank for its TNFa signal across all 3 screens. The top 10 ranked antigens (stimulatory) and 8 of the bottom 10 ranked antigens (inhibitory) were each synthesized as 27mer synthetic long peptides (SLPs) for use in mouse vaccination, as well as four 15mer overlapping peptides (OLPs) for use in ex vivo assays (FIG. 3, Panels A-C).

Example 2, Mouse cancer vaccine study (therapeutic vaccination)

Methods

[0305] The top 8 stimulatory and top 8 inhibitory antigens identified and synthesized in Example 1 were divided into 2 groups of 4 stimulatory antigens and 2 groups of 4 inhibitory antigens, respectively. Individual lyophilized synthetic long peptides (SLPs), 27 amino acids in length, were reconstituted in 50% ACN in H2O and pre-mixed, then frozen and lyophilized for 21h and subsequently frozen again as lyophilized pools. The pools of 4 antigens are denoted Stim 1, Stim 2, Inhib 1, and Inhib 2. These were reconstituted on the day of immunization in either PBS/DMSO or PBS/adjuvants/DMSO (final DMSO concentration: 4%).

[0306] The pools of 4 stimulatory or inhibitory antigens were used to immunize B16F10 tumorbearing mice with or without a triple adjuvant combination (CpG, 3D-PHAD, synthetic saponin), denoted triple adjuvant A, on the following schedule: cancer cells were injected subcutaneously on the right flank on day 0 (ATCC -passage 7, 100K cells in lOOul of 20% Matrigel), vaccine formulations were administered subcutaneously in the tail base on day 3, day 10, and day 17. For SLP-only vaccines, the control group was injected with PBS/DMSO; for adjuvanted vaccines, the control group was injected with triple adjuvant A. A positive control group was injected with 3 published B16F10 antigens: M27 (CD8+ neoantigen), M30 (CD4+ neoantigen), and Trp2 (CD8+ tumor-associated antigen, TAA), previously shown to have both immunogenicity and efficacy in treating the B16F10 tumor model (Castle JC, Kreiter S et al (2012). Exploiting the Mutanome for Tumor Vaccination. Cancer Research 72(5); Kreiter S et al (2015). Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520(7549)). SLPs dosage was 50ug per SLP/mouse/day.

[0307] Heparinized whole blood was collected on day 17 of the study (i.e., 6 days after vaccine injection #2), red blood cells were lysed, and remaining cells resuspended in OpTmizer media. Cells were counted by a Guava instrument, normalized to one cell concentration, and seeded into an IFNy ELISpot plate with overlapping peptides (OLPs; 15mers overlapping by 1 laa) for overnight culture. Cells from each individual mouse sample were split into 2 wells: well 1 contained media alone, well 2 contained pooled OLPs (Ipg/ml) specific to the vaccine that the mouse received. For example, for a mouse immunized with peptide antigens 1-4, the cells were stimulated with OLPs la-d, 2a-d, 3a-d and 4a-d (16 individual 15mers overlapping by 11 aa total).

[0308] Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Mice were euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours. No mice in this study were euthanized for other health reasons.

Results

[0309] As shown in FIG. 4B, mice that were vaccinated with pools of 4 stimulatory or inhibitory antigens (without adjuvant), generally did not secrete IFNy above the PBS/DMSO control level upon re-stimulation. However, as seen in FIG. 4A, mice that were vaccinated with 2 different pools of stimulatory antigens (Stim 1 and Stim 2) combined with triple adjuvant A had vigorous T cell responses to antigen re -stimulation, with responses that were comparable to the positive control (Published). Mice vaccinated with a pool of inhibitory antigens (Inhib 1) combined with triple adjuvant A showed weak IFNy responses in the ELISpot assay.

[0310] Therapeutic immunization with 2 different pools of inhibitory antigens in the absence of adjuvant led to a marked and significant increase in tumor growth kinetics (FIG. 5, Inhib 1 and Inhib 2). On day 14, individual mice that had been immunized with pools of inhibitory antigens (Inhib 1 and Inhib 2) had larger tumors than mice immunized with PBS/DMSO or a pool of stimulatory antigens (lower boxes, FIG. 6C and 6D vs. 6A and 6B). By day 21, more than half or the mice in the Inhib 2 group had to be euthanized due to the size of their tumors (upper box, FIG. 6D), which resulted in the decreased survival rates depicted in FIG. 9A.

[0311] Surprisingly, therapeutic immunization with a pool of inhibitory antigens (Inhib 1) combined with triple adjuvant A led to a slight delay in tumor growth kinetics, most evident after Day 28 relative to adjuvant only (boxes, FIG. 8C compared to FIG. 8A). A modest increase in survival rates relative to adjuvant only was also observed (FIG. 9B, Inhib 1 + adj compared to Adjuvant only). These effects were not discernible in Days 1-18 of the experiment.

[0312] Therapeutic immunization with a pool of stimulatory antigens (Stim 1) combined with triple adjuvant A also led to a delay in tumor growth kinetics relative to adjuvant only (boxes, FIG. 8B compared to FIG. 8A). These mice had better survival relative to adjuvant only (FIG. 9B, Stim 1 + adj compared to Adjuvant only).

[0313] FIG. 7 shows mean tumor area for the groups of mice immunized with pools of stimulatory antigens or inhibitory antigens combined with triple adjuvant A (Stim 1 + adj, Stim 2 + adj, Inhib 1 + adj), the positive control pool of 3 previously known efficacious B16F10 antigens combined with triple adjuvant A (Castle + adj), or triple adjuvant A only.

Example 3, Mouse tumor histology

Methods

[0314] Tumors were harvested from the euthanized mice of Example 2. Briefly, the top 8 stimulatory and top 8 inhibitory antigens identified and synthesized in Example 1 were divided into 2 groups of 4 stimulatory antigens and 2 groups of 4 inhibitory antigens, respectively. The pools of antigens were used to vaccinate B16F10 tumor-bearing mice with or without triple adjuvant A (CpG, 3D-PHAD, synthetic saponin) on the following schedule: cancer cells were injected on day 0, vaccine was injected on day 3, day 10, and day 17. For SLP-only vaccines, the control group was injected with PBS/DMSO; for adjuvanted vaccines, the control group was injected with triple adjuvant A.

[0315] Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Mice were euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours. No mice in this study were euthanized for other health reasons.

[0316] Harvested tumors were fixed with formalin and stained were stained by fluorescent immunohistochemistry for CD8+ (red) with DAPI (blue) as a nuclear counterstain. Tumors were imaged by whole slide scanning and CD8+ T cells were counted by ImageJ software using fluorescent thresholding and size criteria. Graph indicates cell counts from whole tumors.

Results

[0317] FIG. 10 shows fluorescence scans of representative tumor sections from mice immunized with PBS or a pool of inhibitory antigens. Panel (A) shows a fluorescent CD8+ and DAPI stained section of a representative (average) tumor from a mouse immunized with PBS only. Panel (B) shows a fluorescent CD8+ and DAPI stained section of a representative hyper -progressive tumor from a mouse immunized with a pool of inhibitory antigens only. White arrows point to infiltrating CD8+ T cells (red dots). As can be seen from comparison of Panels A and B, the representative hyperprogressive tumor from mice immunized with inhibitory antigens only contains fewer infiltrating CD8+ T cells than the representative tumor from mice immunized with PBS only.

[0318] FIG. 11 is a graph showing mean number of infiltrating CD8+ T cells in whole tumors (N=2) from mice treated with PBS only, or a pool of inhibitory antigens only. As in FIG. 10, hyperprogressive tumors from mice immunized with inhibitory antigens contain substantially fewer infiltrating CD8+ T cells than tumors from mice immunized with PBS only.

[0319] CD8+ T cell infiltration is considered an indication of anti-tumor immunity and correlates to improved prognosis. Reduced CD8+ T cell infiltration may be a contributing factor to observed hyper-progression of tumors.

Example 4, Mouse cancer vaccine study: antigen competition (therapeutic vaccination)

[0320] To assess whether inhibitory antigens can compete with known efficacious antigens and decrease protection against tumors, pools of previously published antigens plus single inhibitory antigens identified in Example 1, combined with a triple adjuvant combination of CpG, 3D-PHAD, and QS-21 (denoted triple adjuvant B or Triple), were used to immunize mice.

Methods

[0321] The 4 inhibitory antigen constituents of the pool denoted Inhib 2, from Example 1, were re-synthesized. Individual lyophilized SLPs were reconstituted in 50% ACN in H2O and a portion pre-mixed, then frozen and lyophilized for 48h and subsequently frozen again as individual peptides and lyophilized pools. These were reconstituted on the day of immunization in either PBS/DMSO or PBS/adjuvants/DMSO (final DMSO concentration: 4%). The known efficacious antigens were as noted in Example 2: M27 (CD8⁺ neoantigen), M30 (CD4⁺ neoantigen) and Trp2 (CD8⁺ tumor- associated antigen, TAA), shown to have both immunogenicity and efficacy in treating the Bl 6F 10 tumor model (Castle JC, Kreiter S et al (2012). Exploiting the Mutanome for Tumor Vaccination. Cancer Research 72(5); Kreiter S et al (2015). Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520(7549))

[0322] B16F10 tumor-bearing mice were vaccinated on the following schedule: cancer cells were injected subcutaneously on the right flank on day 0 (ATCC -passage 6, 100K cells in 100 pl of 20% Matrigel), vaccine was injected subcutaneously at the tail base on day 3, day 10, and day 17. The experimental groups were injected with: 1) a pool of 2 previously known efficacious B16F10 antigens, denoted Published: M30 (CD4⁺ neoantigen) and Trp2 (CD8⁺ tumor-associated antigen, TAA), with triple adjuvant B; 2) the same pool as 1) plus all 4 inhibitory antigens of the Inhib 2 pool (described in Example 1), with triple adjuvant B; 3-4) the same pool as 1) plus one each of two of the 4 inhibitory antigen constituents of the Inhib 2 pool (In21, Inl7), with triple adjuvant B. The control group was injected with triple adjuvant B only. SLPs dosage was 50pg per SLP/mouse/day.

[0323] Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Mice are euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours.

Results

[0324] FIG. 12 shows that addition of an inhibitory antigen can significantly abrogate protective effects of known efficacious antigens. In Panel A, immunization with a pool comprising inhibitory antigen In21 and known efficacious antigens reversed the protection from tumor growth observed with the pool of known efficacious antigens alone (Published), to a greater degree even than the adjuvant-only negative control. Panel B shows variability in the deleterious effects of inhibitory antigens. Immunization with a pool comprising inhibitory antigen Inl7 and known efficacious antigens resulted in slight reduction of protection.

Example 5, Mouse cancer vaccine study II (therapeutic vaccination)

Methods

[0325] The 4 inhibitory antigen constituents of the pool denoted Inhib 2, from Example 1, were re-synthesized. Individual lyophilized SLPs were reconstituted in 50% AON in H2O and pre-mixed, then frozen and lyophilized for 48h and subsequently frozen again as lyophilized pools. These were reconstituted on the day of immunization in either PBS/DMSO or PBS/adjuvants/DMSO (final DMSO concentration: 4%).

[0326] The Inhib 2 pool of 4 inhibitory antigens was combined with triple adjuvant B (CpG, 3D- PHAD, QS21) and used to immunize B16F10 tumor-bearing mice on the following schedule: cancer cells were injected subcutaneously on the right flank on day 0 (ATCC -passage 6, 100K cells in lOOul of 20% Matrigel), vaccine formulations were administered subcutaneously in the tail base on day 3, day 10, and day 17. The control group was injected with triple adjuvant B only. SLPs dosage was 50ug per SLP/mouse/day. Triple adjuvant B dosage was CpG (5ug/mouse), 3D-PHAD (5ug/mouse), and QS21 (25ug prime, 12.5ug boost/mouse).

[0327] Heparinized whole blood was collected on day 17 of the study (i.e., 6 days after vaccine injection #2), red blood cells were lysed, and remaining cells resuspended in OpTmizer media. Cells were counted by a Guava instrument, normalized to one cell concentration, and seeded into an IFNy ELISpot plate with stimulants for overnight culture. Cells from each individual mouse sample were split into 2 wells: well 1 contained media alone, well 2 contained pooled OLPs (Ipg/ml) specific to the vaccine that the mouse received, i.e., for a mouse immunized with peptide antigens 5-8 (Inhib 2 pool), the cells were stimulated with OLPs 5a-d, 6a-d, 7a-d and 8a-d (16 individual 15mers overlapping by 1 laa total).

[0328] Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Mice were euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours. No mice in this study were euthanized for other health reasons.

Results

[0329] FIG. 13 shows results of therapeutic immunization with the Inhib 2 pool of 4 inhibitory antigens combined with triple adjuvant B. Approximately half of the immunized mice had a marked and significant increase in tumor growth kinetics (hyper-progression), as compared to control immunization with triple adjuvant B only. Hyper-progression correlated with lower IFNy secretion, i.e., lower immune response. Results for Panels A-B are expressed as tumor volume in mm³ over time. Panel A shows mean curves for the two immunization groups. Panel B shows curves for individual mice in the two immunization groups. Panels C and D show the correlation between tumor volume in mm³ and IFNy spot forming units per 200K cells. These results contrast with results obtained for the Inhib 1 pool combined with triple adjuvant A (CpG, 3D-PHAD, synthetic saponin) shown in FIG. 8, suggesting that hyper-progression may be adjuvant-dependent, antigen-dependent, or both.

Example 6, Differential Impact of Adiuvanted Inhibitory Antigens on Tumor Growth in Mice

Methods

[0330] The 4 inhibitory antigen constituents of the pool denoted Inhib 2, from Example 1, were re-synthesized. Individual lyophilized SLPs were reconstituted in 50% ACN in H2O and pre-mixed, then frozen and lyophilized for 48h and subsequently frozen again as lyophilized pools. These were reconstituted on the day of immunization in either PBS/DMSO or PBS/adjuvants/DMSO (final DMSO concentration: 4%).

[0331] Pools of 4 inhibitory antigens were used to vaccinate B16F10 tumor-bearing mice with or without the following adjuvants: 1) incomplete Freund’s adjuvant (IF A); 2) CpG; 3) poly-IC; or 4) triple adjuvant B (CpG, 3D-PHAD, QS-21). The following schedule was employed: cancer cells were injected on day 0 (ATCC -passage 6, 100K cells in 100p.l of 20% Matrigel, subcutaneously on the right flank). Vaccine was injected on day 3, day 10, and day 17. Control groups were injected with PBS or each adjuvant alone, in the absence of antigens. Fifteen mice per group were evaluated. SLP dosage was 5 Opig per SLP/mouse/day . Adjuvant dosage per mouse per day was: IFA = 1:1 emulsion with antigens; CpG (5pg); poly-IC (5 pg); triple adjuvant B = prime: QS-21 (25 pg), 3D- PHAD (5pg), CpG (5pg) and boost: QS-21 (12.5pg), 3D-PHAD (5pg), CpG (5 pg). The final formulated vaccines were injected by subcutaneous tail base injection (50pl on each side of the tail base for a total of 100 pl).

[0332] Blood was drawn by retro-orbital bleed on day 17 of the study (i.e., 6 days after vaccine injection #2), red blood cells were lysed, and remaining cells resuspended in OpTmizer media. In addition, in a subset of mice, spleens and draining lymph nodes were collected between days 20-35. Cells were counted by a Guava instrument, normalized to one cell concentration, and seeded onto an IFNy ELI Spot plate with stimulants for overnight culture. Each individual mouse blood or cell sample was split into 2 wells, and stimulated with media only or with overlapping peptides (OLPs; 15mers overlapping by 11 aa) spanning each of the vaccine antigens. Each OLP was used at 1 pg /ml in the overnight ELISpot culture plate.

[0333] Tumor size was measured 3x per week and subsequently on a daily basis after reaching a specified size threshold (2000mm³). Mice were euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours. No mice in this study were euthanized for other health reasons.

Results

[0334] As shown in FIG. 14, mice that were vaccinated with pools of 4 inhibitory antigens with or without adjuvant generally did not secrete IFNy above the adjuvant-only control level upon stimulation. The one exception was mice that were vaccinated with antigens combined with triple adjuvant B, where there was a statistically significant increase in cytokine secretion from peripheral blood T cells in response to vaccination. The effect was observed in approximately half of the mice, i.e., half responded, and half failed to respond. The same was true for splenocytes (FIG. 15) and lymph node cells (FIG. 16) evaluated from a subset of mice in the study; there was a large increase in the proportion of cells secreting IFNy in about half of the mice evaluated in the group immunized with inhibitory antigens and triple adjuvant B. None of the other adjuvants induced stimulatory T cell responses in splenocytes or lymph node cells of the immunized tumor-bearing mice.

[0335] Strikingly, therapeutic immunization with different adjuvants led to different kinetics of tumor growth. Consistent with the immunogenicity data shown in FIG. 14-16, mice that received inhibitory antigens with triple adjuvant B showed slightly reduced tumor growth kinetics compared to mice that received triple adjuvant B only. The growth curves in FIG. 17 show a delay of tumor growth in mice with tumors exceeding 500mm² (day 14 for adjuvant only and day 17 for adjuvant plus antigens), as well as no mice reaching tumor sizes exceeding 1500mm² by day 18, and fewer mice reaching 1000mm² or exceeding 1500mm² by day 21 in the antigen-containing group. In contrast, as shown in FIG. 18, on day 7, mice vaccinated with inhibitory antigens adjuvanted with poly-IC had marked increase in tumor size relative to mice who received poly-IC only (or any of the other groups). This effect was maintained throughout the time-course, although the fold-change decreased with time. Similarly, mice that received unadjuvanted inhibitory antigens or inhibitory antigens adjuvanted with IFA had larger tumor sizes relative to mice that received PBS or IFA only, respectively. By day 17 of the study, mice that received inhibitory antigens adjuvanted with IFA maintained tumor sizes that were 1.5-fold higher than their IFA only counterparts. In contrast, there was essentially no difference in tumor growth between mice that received CpG with inhibitory antigens and those that received CpG alone. FIG. 19 shows the correlation between tumor volume in mm³ and IFNy spot forming units per 200K cells for the Inhib 2 + triple adjuvant B immunization group. As in Example 9, hyperprogression correlated with lower IFNy secretion, i.e., lower immune response.

[0336] Taken together, these results demonstrate that immune responses and control of tumor growth in response to vaccination with inhibitory antigens are malleable. With the appropriate adjuvant, responses to inhibitory antigens that impair or reduce immune control of tumors can be abrogated.

Example 7, Tumor histology following vaccination with inhibigens

[0337] To further characterize the effects of vaccination with inhibigens, pools of previously published stimulatory antigens plus single inhibitory antigens were used to immunize mice, similarly to Example 8. Resulting tumors were then examined by histological methods.

Methods

[0338] Synthetic Long Peptides (SLPs) corresponding to inhibitory antigens and to previously known stimulatory antigens were synthesized. Individual lyophilized SLPs were reconstituted in 50% ACN in H₂O and a portion pre-mixed, then frozen and lyophilized for 48h and subsequently frozen again as individual peptides and lyophilized pools. These were reconstituted on the day of immunization in PBS/DMSO/adjuvant (final DMSO concentration: 4%). The inhibitory antigen used in this study was MMP9FS, denoted In21, from the Inhib 2 pool described in Example 1.

[0339] In21 is a murine MMP9 frameshift mutation identified in SEQ ID NO: 453. The mutated sequence is VFFFSGRKCGCTQARPCWAPGVWISWV (SEQ ID NO: 453) and the wildtype sequence is VFFFSGRQMWVYTGKTVLGPRSLDKLG (SEQ ID NO: 454).

[0340] Previously known stimulatory antigens used in this study were M30 (CD4⁺neoantigen) and Trp2 (CD8⁺ tumor-associated antigen, TAA), have been shown to have both immunogenicity and efficacy in treating the Bl 6F 10 tumor model (Castle JC, Kreiter S et al (2012). Exploiting the Mutanome for Tumor Vaccination. Cancer Research 72(5); Kreiter S et al (2015). Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520(7549)). The adjuvant used in this study was a triple adjuvant combination of CpG, 3D-PHAD, and QS-21, denoted triple adjuvant B.

[0341] B16F10 tumor-bearing mice were vaccinated on the following schedule: cancer cells were injected subcutaneously on the right flank on day 0 (ATCC -passage 6, 100K cells in lOOpl of 20% Matrigel), vaccine was injected subcutaneously at the tail base on day 3, day 10, and day 17. The experimental groups were injected with: 1) protective vaccine: a pool of previously known stimulatory B16F10 antigens M30 (CD4⁺ neoantigen) and Trp2 (CD8⁺ tumor-associated antigen, TAA), with triple adjuvant B; or 2) the same protective vaccine plus inhibitory antigen In21, with triple adjuvant B. The control group was injected with triple adjuvant B only. SLP dosage was 50 pg per SLP/mouse/day.

[0342] Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Mice were euthanized when tumors reached maximum size, or became ulcerated and did not heal within 24 hours. No mice in this study were euthanized for other health reasons.

[0343] Harvested tumors were fixed with formalin and were stained by chromogenic immunohistochemistry. Tumors were imaged by whole slide scanning and CD8⁺ T cells were counted by ImageJ software using fluorescent thresholding and size criteria. Expression of the surface expression markers PD-1 and Lag3, associated with T cell inhibition and T cell exhaustion, was measured by flow cytometry.

Results

[0344] FIG. 20, Panel A shows color scans of representative tumor sections from mice immunized with triple adjuvant B only (left), protective vaccine (center), or protective vaccine plus inhibigen In21 (right). Tumor sections were formalin-fixed, paraffin-embedded, stained by chromogenic immunohistochemistry (IHC) with an anti-mouse CD8a antibody, and counterstained for nuclei with hematoxylin. Endogenous melanin deposits in tumors are visible. Fewer infiltrating CD8+ T cells are seen in the tumor taken from protective vaccine plus inhibigen-treated mice (right) relative to protective vaccine-treated mice (center).

[0345] Panel B is a graph showing mean number of infiltrating CD8⁺ T cells from multiple lOx fields per tumor isolated from mice of each vaccination group. Fewer infiltrating T cells are observed in tumors isolated from the group vaccinated with protective vaccine plus inhibigen.

[0346] Tumor replicates: adjuvant (5), protective vaccine (5), protective vaccine plus inhibigen In21 (9). *p = 0.0123, **p = 0.0079. [0347] Panel C is a graph showing flow cytometry results for CD4+ and CD8+ T cells expressing the inhibitory surface markers PD-1 and Lag3. T cells were isolated from 4 pooled tumors per vaccination group. Inhibitory surface markers were elevated in T cells isolated from the group vaccinated with protective vaccine plus inhibigen, particularly CD8⁺ T cells. MFI = mean fluorescence intensity.

[0348] Together, these results show that vaccination with an inhibigen can alter the tumor microenvironment, reducing T cell infiltration and elevating T cell inhibitory surface marker expression.

Example 8, Effects of inhibigen vaccination on T-regulatorv cells

Methods

[0349] To determine whether vaccination with inhibigens exerts an effect on T-regulatory cells (T-regs), expression of the T-regulatory marker Foxp3 was examined both in tumors and in draining lymph nodes harvested from euthanized mice of Example 11.

Results

[0350] FIG. 21, Panel A shows a representative flow cytometry analysis of draining lymph nodes from 4 pooled mice per vaccination group. In the left graph, CD4⁺ Foxp3⁺ cells are delineated

+ + by boxes. In the right graph, CD4 Foxp3 cells are shown as a percentage of total cells in the draining lymph node population.

[0351] Panel B shows color scans of representative tumor sections from mice immunized with triple adjuvant B only (left), protective vaccine (center), or protective vaccine plus inhibigen In21 (right). Tumor sections were formalin-fixed, paraffin-embedded, stained by chromogenic immunohistochemistry (IHC) with an anti-mouse Foxp3 antibody and counterstained for nuclei with hematoxylin. Endogenous melanin deposits in tumors are visible.

[0352] Panel C shows autologous dendritic and T cells from a representative human cancer patient, co-cultured and screened against stimulatory (2 wells) and inhibitory (5 wells) patient-specific antigens previously identified on the ATLAS platform. 24 hrs post co-culture, cells within the well were harvested and flow cytometry analysis of the T cells subsets performed for CD3, CD4, CD8, and Foxp3 positive T cell subsets. Data is representative of multiple wells containing T cells responsive to a stimulatory antigen, inhibigen, or control. These data show that wells where inhibigen responses were obtained do not contain more inhibitory T-regulatory cells than wells where stimulatory responses were obtained. [0353] These results show that there is no difference in T-regulatory cell numbers between experimental vaccination groups or in a representative cancer patient screened for responses to stimulatory antigens and inhibigens. These data suggest that the inhibigen mechanism of action is not mediated by increased abundance of T-regulatory cells in the tumor or periphery in mice, nor by increased T-regulatory cell expansion in human screens.

Example 9, Effects of inhibigen vaccination on INFY cytokine responses

Methods

[0354] To determine whether vaccination with inhibigens exerts an effect on IFNy cytokine responses, IFNy ELISpot assays were performed on splenocytes isolated from mice of Example 11. The whole splenocytes were stimulated with overlapping peptides corresponding to antigens of the protective vaccine, M30 and Trp2, the protective vaccine plus inhibigen In21, or with media as a control. Additionally, T cell percentages were determined via flow cytometry, and lymphocytes from the draining lymph nodes counted and viability determined by counting cassettes using acridine- orange (for viability) and DAPI (for nuclei) via the Nucleocounter cell counter.

Results

[0355] FIG. 22, Panel A shows results of representative IFNy ELISpot assays using splenocytes isolated from mice vaccinated with protective vaccine or protective vaccine plus inhibigen In21. Results are expressed as the IFNy spot forming cells (SFC) per IxlO⁶ splenocytes.

[0356] Panel B shows representative viability of lymphocytes isolated from draining lymph nodes, which was consistent across groups. Lymphocytes were counted in draining lymph nodes from mice of each vaccination group (n = 4 mice per group). Viability of the lymphocytes was determined directly ex vivo using counting cassettes containing viability dye (see above).

[0357] Panel C shows representative flow cytometry analysis of splenocytes isolated from mice of each vaccination group and re-stimulated with overlapping peptides corresponding to the protective vaccine antigens M30 and Trp2 (Stim), or to M30, Trp2 and inhibigen In21 (Inhib). Gating

+ was on total CD3 T cells, and is presented as percent of total cells.

[0358] These results show that vaccination with an inhibigen leads to decreased antigen specific T cell IFNy cytokine responses and that the decrease in IFNy cytokine responses is not attributable to a decrease in T cell viability or number.

Example 10. Effects of inhibigen vaccination on cytolytic activity of T cells [0359] A luminescent T cell killing assay was performed by pulsing RAW309 target cells with peptides corresponding to antigens of the protective vaccine M30 and Trp2 or to M30, Trp2 and inhibigen In21. The pulsed target cells were then co-cultured at different ratios with whole splenocytes isolated from mice of Example 11. Splenocytes were pooled from 4 mice per vaccination group.

[0360] FIG. 23 shows results of a representative killing assay, expressed as percent cytotoxicity for T cells of each vaccination group, plotted against ratio of splenocytes co-cultured with pulsed target cells (RAW309s) (denoted as E:T ratios 40:1, 20:1, 10:1). Error is the difference among replicate wells. *p = 0.028 **p=.0002.

[0361] These results show that vaccination with an inhibigen results in T cells that fail to kill target cells, i.e., are deficient in cytolytic activity, even when the inhibigen is administered with known stimulatory antigens.

Example 11. Effects of inhibigen vaccination on global IFNY expression

[0362] To determine whether vaccination with inhibigens exerts a global effect on IFNy cytokine responses, IFNy ELISpot assays and intracellular flow cytometry were performed on splenocytes isolated from mice of Example 11. The whole splenocytes were stimulated with anti- CD3 monoclonal antibodies (anti-CD3), or with phorbol myristate acetate (PMA) as a positive control. Splenocytes were pooled from 4 mice per vaccination group.

[0363] FIG. 24, Panel A shows representative PMA-stimulated ELISpot wells (left) and intracellular flow cytometry analysis of splenocytes after stimulation with anti-CD3 monoclonal antibody (right) for each vaccination group. IFNy⁺CD3⁺ T cells are delineated by boxes.

[0364] Panel B corresponds to the flow cytometry analysis of Panel A, and charts the percentage of IFNy+ T cells for each vaccination group.

[0365] These results show that vaccination with an inhibigen results in global depression of IFNy cytokine production by T cells.

Example 12, Effects of inhibigen vaccination on immune response to a different antigen

[0366] Tumors from mice of Example 11 (n = 2 mice from each vaccination group) were pooled, harvested, minced, digested with collagenase and DNAse, and plated on tissue culture (TC) treated flasks overnight. After 24 hrs, the supernatants and suspension cells were sorted for + +

CD4 /CD8 tumor infiltrating lymphocytes using Miltenyi microbeads technology. Trp2 tetramer- specific cells were then identified using a Trp2 tetramer which expresses MHC loaded with a specific Trp2 peptide.

[0367] FIG. 25 shows representative results of a sorting experiment. CD8 tumor infiltrating lymphocytes (CD8⁺, x axis) that react with Trp2 tetramer (Trp2-tet, y axis), and therefore express the T cell receptor for Trp2, are delineated by hexagons. For each vaccination group, the Median Fluorescence Intensity of these cells is:

[0368] Adjuvant only: 7,956

[0369] Protective vaccine: 7,688

[0370] Protective vaccine plus inhibigen In21: 2,457

[0371] These results show that vaccination with an inhibigen (In21) decreases specific immune response to a previously known stimulatory antigen (Trp2), including down -regulation of the T cell receptor on Trp2-specific T cells.

Example 13, Studies 1 and 2: Effects of inhibigen vaccination on Experimental Autoimmune Encephalomyelitis (EAE) induced by MOG peptide

[0372] Multiple sclerosis (MS) is an inflammatory, T-cell mediated (1) autoimmune disease of the CNS that can lead to substantial disability in affected individuals (2). MS causes nerve cell demyelination and destruction of oligodendrocytes, neurons and axons (3, 4) with varied clinical presentation and undefined etiology. There is no cure for MS, and though there are FDA-approved treatments for relapsing-remitting and chronic-progressive variants of disease, no such therapies exist for patients who present with acute illness (5).

[0373] CD4+ T cell-mediated Experimental Autoimmune Encephalomyelitis (EAE) is the classical animal model of MS, and stimulation of an autoimmune response against CNS antigens is the underlying mechanism of EAE (6). This immune response can be induced by active induction, in which animals are immunized with purified or recombinant myelin proteins, or synthetic peptides derived from these proteins, emulsified in Complete Freund’s Adjuvant (CFA). Once EAE is induced, animals develop either acute or chronic progressive forms of the disease. The progression of the disease is evaluated and scored with a 5 -point scoring scale that evaluates muscle tone in the tail and limbs (7).

[0374] Objective: The objective of these two studies was to evaluate the modulation of experimental autoimmune encephalomyelitis (EAE) by the MMP9FS peptide (described in Example 6), co-formulated with the MOG35-55 peptide. The studies were performed in C57B1/6 mice. [0375] Study 1 Design: On Day 0, 36 mice (Groups 2-4; n=12 per group) were administered two subcutaneous (SC) injections at two sites on the back (upper and lower) of 0.1 mL (per site; 0.2 mL per mouse) myelin oligodendrocyte glycoprotein 35-55 (MOG35-55; 400 pg total; 200 pg per site) emulsified in Complete Freund’s Adjuvant (CFA; 5 mg killed mycobacterium tuberculosis H37Ra/mL emulsion). For Group 3, the MOG35-55 peptide was co-formulated with DMSO. For Group 4, the MOG35-55 peptide was co-formulated with DMSO and MMP9FS peptide (50 pg dose). Animals in Group 5 received MMP9FS peptide alone emulsified with CFA (50 pg dose no MOG), administered at 2 sites on the back SC (0.1ml each). Animals in Group 1 (n=5) served as naive controls.

[0376] Approximately 1-2 hours after the above, mice were intraperitoneally (IP) injected with 200 ng Pertussis toxin (PTx) in 0.1 mL PBS (2 pg/mL). An additional IP injection with PTx was given on Day 2.

[0377] Groups of Study 1 are summarized in Table 3.

Table 3. Experimental Groups of Study 1

[0378] Study 2 Design: On Day 0, 30 mice (Groups 2-4; n=10 per group) were administered two subcutaneous (SC) injections at two sites on the back (upper and lower) of 0.1 mL (per site; 0.2 mL per mouse) myelin oligodendrocyte glycoprotein 35-55 (MOG35-55; 200 pg total; 100 pg per site) emulsified in Complete Freund’s Adjuvant (CFA; 5 mg killed mycobacterium tuberculosis H37Ra/mL emulsion). For Group 2, the MOG35-55 peptide was co-formulated with DMSO. For Group 3, the MOG35-55 peptide was co-formulated with DMSO and MMP9FS peptide at IX dose (50 pg). For Group 4, the MOG35-55 peptide was co-formulated with DMSO and MMP9FS peptide at 4X dose (200 pg). Animals in Group 5 received MMP9FS peptide alone emulsified with CFA (200 pg dose, no MOG), administered at 2 sites on the back SC (0.1ml each). Animals in Group 1 (n=5) served as naive controls. [0379] Approximately 1-2 hours after the above, mice were intraperitoneally (IP) injected with 200 ng Pertussis toxin (PTx) in 0.1 mL PBS (2 pg/mL). An additional IP injection with PTx was given on Day 2.

[0380] Groups of Study 2 are summarized in Table 4.

Table 4. Experimental Groups of Study 2

[0381] For both Study 1 and Study 2: Animals were weighed daily for the duration of the experiment. EAE severity was assessed daily beginning on Day 4, according to the scoring scale shown in Table 5. Mice that reached an EAE score of five (tetraplegia), reached a score of four on two consecutive days, or had lost 30% of their initial body weight were euthanized. Collections were performed for unscheduled euthanasia.

Table 5: EAE Scoring Scale

[0382] FIG. 26 shows a representative time course for EAE disease progression for groups of naive mice and mice receiving MOG35-55, MOG35-55 + MMP9FS, or MMP9FS (Study 2). Results are plotted as the EAE disease score (mean +/-SEM) for each group against study day. FIG. 27 shows representative disease-free incidence curve for groups of naive mice and mice receiving MOG35-55, MOG35-55 + MMP9FS, or MMP9FS (Study 2). Results are plotted as the percent disease-free incidence for each group against study day. Co-administration of MMP9FS with MOG35-55 resulted in a marked decreased of both EAE disease severity and EAE disease incidence.

[0383] For both Study 1 and Study 2: All animals were sacrificed at the completion of the study on Day 35. Blood was collected for serum preparation. Serum was stored at -80°C. The spinal cord was collected in-vertebrae and stored in formalin for downstream histopathological analysis. Spleens were collected in RPMI media on ice.

[0384] Immunogenicity assays: Resected spleens were processed and incubated in overnight assays with either media, overlapping 15mer peptides spanning the MOG35-55 and MMP9FS peptides used in vaccination, or PMA/ionomycin. ELISpot for IFN-gamma revealed levels of T cell responses to re -stimulation with peptides used in vaccination. Supernatants from ELISpot assays were collected and further assayed by cytokine bead arrays for additional cytokines of interest: IL2, IL4, IL6, IL10, IL 17a, and TNF-alpha, quantified by flow cytometry.

[0385] FIG. 28 shows representative results of immunogenicity assays. Panel A shows IFN- gamma ELISpot results for Study 1. Panel B shows IFN-gamma ELISpot results for Study 2. IFN- gamma levels are expressed as spots per 400K splenocytes. Panel C shows flow cytometry results of Study 2 for additional cytokines IL2, IL4, IL6, IL10, IL17a, and TNF-alpha, following re -stimulation with the MOG35-55 peptide. Cytokine levels are expressed in pg/ml supernatant. Each symbol represents an individual mouse; horizontal lines indicate the mean +/- SEM. In each case, comparison of the MOG35-55 and MOG35-55 + MMP9FS groups re-stimulated with MOG35-55 demonstrated that coadministration of MMP9FS with MOG35-55 impaired immunogenicity of MOG35-55. [0386] Spinal cord pathology: Resected spinal cords were fixed in 10% formalin followed by 70% ethanol, removed from the spinal column, and embedded in paraffin for sectioning onto glass slides. These were then stained by chromogenic immunohistochemistry (IHC) for markers of interest including: MOG (myelin oligodendrocyte glycoprotein), CD4 (helper T cells), CD8 (cytotoxic T cells), Iba-1 (microglia), F4/80 (macrophages), and CD19 (B cells). MOG staining indicates levels of myelin coverage, or demyelination, in spinal cords. Immune cell markers CD4, CD8, Iba-1, F4/80 and CD 19 indicate immune cell infiltration and/or expansion, associated with inflammation of the spinal cords. IHC images were quantified by ImageJ software.

[0387] FIG. 29 shows myelin coverage and immune cell infiltration in myelinated ( Panel A) and demyelinated (Panel B) spinal cord sections, visualized by IHC staining for the indicated markers (Study 1). FIG. 30 presents quantitative results for myelin coverage and immune cell infiltration, expressed as the percent area of myeloid IHC staining. FIG. 31 shows myelin coverage in spinal cord sections, visualized by IHC staining for MOG (black arrows; Study 2). FIG. 32 shows microglia present in spinal cord sections, visualized by IHC staining for Iba-1 (Study 2). FIG. 33 presents quantitative results for myelin coverage and immune cell infiltration, expressed as the percent area of myeloid IHC staining. The results show that co-administration of MMP9FS with MOG35-55 resulted in (i) diminished infiltration of CD4+ T cells, CD 19+ B cells, F4/80+ macrophages, and Iba-1 + microglia, and (ii) absence of demyelination, on visual scoring of spinal cord sections IHC stained for MOG. Quantitation of MOG staining was not informative compared to visual scoring, because demyelination occurs only at the margin of spinal cord sections, while the rest of the sections stain positive.

[0388] These studies show that a previously identified inhibitory antigen (MMP9FS) can dampen deleterious immune responses in an animal model of multiple sclerosis. Inhibitory antigens may therefore be useful therapeutic agents in the context of autoimmune disease.

[0389] References:

Goverman, J. 2009. Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9: 393-407.

Rodriguez, M.a, A. Siva, J. Ward, K. Stolp-Smith, P. O’Brien, and L. Kurland. 1994. Impairment, disability, and handicap in multiple sclerosis: a population-based study in Olmsted County, Minnesota. Neurology 44: 28-33.

Dutta, R., and B.D. Trapp. 2007. Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 68: S22-31; discussion S43-54.

Frohman, E.M., M.K. Racke, and C.S. Raine. 2006. Multiple sclerosis - the plaque and its pathogenesis. N Engl J Med 354: 942-955. Goldenberg, M.M. 2012. Multiple sclerosis review. P T 37: 175-184.

Friese, M.A., X. Montalban, N. Wilcox, J. I. Bell, R. Martin, and L. Fugger. 2006. The value of animal models for drug development in multiple sclerosis. Brain 129: 1940-1952.

Ben-Nun, A., N. Kaushansky, N. Kawakami, G. krishnamoorthy, K. Berer, R. Liblau, R. Hohlfeld, and H. Wekerle. 2014. From classic to spontaneous and humanized models of multiple sclerosis: impact on understanding pathogenesis and drug development. J Autoimmun 54: 33-50.

Example 14, Adoptive transfer of in v/vo-primed, antigen-specific T cells

[0390] ATLAS methods were extended to adoptive cell therapy by selectively expanding in vivo, through vaccination with vaccines comprising ATLAS -identified antigens, T cells that are likely to enhance immune control of tumors, or conversely, to inhibit or suppress immune control of tumors. These data provide proof-of-concept for the use of T cells specific to inhibitory antigens, expanded in vivo or ex vivo, to dampen, inhibit or suppress immune responses in subjects suffering from an autoimmune disease or overactive immune condition.

Preliminary data:

[0391] A vaccine comprising ATLAS-identified stimulatory antigens elicited significant T cell responses and showed anti-tumor efficacy against B16F10 tumor challenge in mouse studies (PCT/US2019/053672, filed September 27, 2019). Strikingly, therapeutic immunization with inhibitory antigen peptides led to a marked and significant increase in tumor growth kinetics. These data demonstrate the ability of the ATLAS platform to identify and characterize both immune - enhancing and immune-inhibitory or immune-suppressing antigen-specific T cell responses in an aggressive in vivo mouse tumor model.

Design of the study:

[0392] In this study, C57BL/6 mice 6-8 weeks of age were injected subcutaneously in the anterior right flank with B16F10 melanoma cells (1 x 10⁵ tumor cells/mouse). Three days after tumor implantation, mice were immunized with 1) a vaccine comprising 3 previously known stimulatory B16F10 antigens (ATLAS-identified Gal3stl + M30 + Trp2, labeled Protective), 2) a vaccine comprising an inhibitory antigen alone (MMP9FS) formulated with a triple adjuvant combination (CpG, 3D-PHAD, synthetic saponin), or 3) adjuvant alone, and then boosted once on day 10. On Day 15, mice were euthanized, and their draining lymph nodes and spleens harvested and pooled within groups. For each group, T cells were sorted using magnetic beads (CD3+). In parallel, on day 15, a new group of athymic B6 Nude mice 6-8 weeks of age were injected subcutaneously in the anterior right flank with B16F10 melanoma cells (1 x 10⁵ tumor cells/mouse) and concurrently received an intravenous adoptive transfer of CD3+ T cells sorted from vaccinated donor animals. T cells were transferred in separate or mixed groups. T cells were mixed for adoptive transfer as follows: 1 x 10⁶ adjuvant T cells + 1 x 10⁶ protective (Gal3stl/M30/Trp2) T cells, or 1 x 10⁶ protective + 1 x 10⁶ inhibitory (MMP9FS) T cells.

[0393] Efficacy was monitored kinetically using tumor measurements, flow cytometry, immunohistochemistry, and ELISpot assays. Tumor size was measured 3x per week and subsequently on a daily basis, after reaching a specified size threshold. Both donor mice and recipient mice were euthanized when tumors reached maximum size or became ulcerated and did not heal within 24 hours. Data are represented as the mean ± SEM from 8 mice per group, in mm³ graphed against days post-tumor injection (for donor mice) or days post-tumor injection + adoptive transfer (for recipient mice). No mice in this study were euthanized for other health reasons.

[0394] For donor mice, cytokine responses indicating T cell activation were measured by ELISpot assays performed on splenocytes isolated from spleens and lymph nodes. The isolated splenocytes were stimulated with overlapping peptides corresponding to stimulatory antigens (Gal3stl, M30, Trp2), the inhibitory antigen MMP9FS, media as negative control, or phorbol myristate acetate/ionomycin (PMA/iono) as positive control. IFNy levels are expressed as spots per 400K splenocytes.

[0395] For recipient mice, cytokine responses indicating T cell activation were assessed by flow cytometry. Spleens were resected from recipient mice of each group, stimulated overnight with peptides spanning stimulatory antigens (Gal3stl, M30, Trp2), then analyzed by flow cytometry. IFNy and 11-2 responses are reported as the total percentage of CD4+ and CD8+ T cells responsive to stimulation (mean ± SEM from 4 mice per group).

Results:

[0396] FIG. 34, Panels A and B show a diagram of methods, together with representative results, of the study. Panel A shows expected tumor growth (center) and IFNy responses (bottom) in donor mice following tumor injection and vaccination with a vaccine comprising immune stimulatory antigens, a vaccine comprising the inhibitory antigen MMP9FS , or adjuvant alone. As previously shown, vaccination with an inhibitory antigen broadly reduced T cell activation, as measured by IFNy responses, and led to accelerated tumor growth, indicating inhibition or suppression of immune responses. [See, for example, WO 2018/175505.] Panel B shows tumor growth in recipient mice, following tumor injection and adoptive transfer of T cells from donor mice of Panel B. Panel C shows T cell activation in recipient mice, as measured by IFN-g and 11-2 responses.

[0397] In recipient mice, a transferred mixture of T cells from donor mice vaccinated with vaccine comprising stimulatory antigens and vaccine comprising an inhibitory antigen led to significantly larger tumors, as compared to a mixture of T cells from donor mice vaccinated with vaccine comprising stimulatory antigens and adjuvant-only treatment. Because recipient mice of both groups received the same number of stimulatory antigen-specific T cells, these data demonstrate that inhibitory antigen-specific donor T cells actively inhibited or suppressed immune control of tumors in the recipient mice. Ex vivo re -stimulation of T cells populations isolated from recipient mice recapitulated the reduced cytokine production observed in inhibitory antigen-specific T cells of donor mice. Thus, inhibitory antigen-specific donor T cells may be used to inhibit or suppress immune responses. In the context of autoimmune diseases or overactive immune conditions, inhibition or suppression of immune responses is a desirable outcome.

LISTING OF SEQUENCES

Listeriolysin O(Listeria monocytogenes) NP_463733.1 GI:16802248 (SEQ ID

NO: 1)

MKKIMLVFITLILVSLPIAQQTEAKDASAFNKENSISSMAPPASPPASPKTPIEKKHADEIDKYIQGLD YNKNNVLVYHGDAVTNVPPRKGYKDGNEYIWEKKKKSINQNNADIQWNAISSLTYPGALVKANSELVENQPDV LPVKRDSLTLSIDLPGMTNQDN KIWKNATKSNVNNAVNTLVERWNEKYAQAYPNVSAKIDYDDEMAYSESQLIAKFGTAFKAVNNSLNVNFGAISE GKMQEEVISFKQIYYNVNVNEPTRPSRFFGKAVTKEQLQALGVNAENPPAYISSVAYGRQVYLKLSTNSHSTKVK AAFDAAVSGKSVSGDVELTNIIKNSSFKAVIYGGSAKDEVQIIDGNLGDLRDILKKGATFNRETPGVPIAYTTNF LKDNELAVIKNNSEYIETTSKAYTDGKINIDHSGGYVAQFNISWDEVNYDPEGNEIVQHKNWSENNKSKLAHFTS SIYLPGNARNINVYAKECTGLAWEWWRTVIDDRNLPLVKNRNISIWGTTLYPKYSNKVDNPIE Listeriolysin O (A3-25) (SEQ ID NO:2)

MKDASAFNKENSISSMAPPASPPASPKTPIEKKHADEIDKYIQGLDYNKNNVLVYHGDAVTNVPPRKGY KDGNEYIWEKKKKSINQNNADIQWNAISSLTYPGALVKANSELVENQPDVLPVKRDSLTLSIDLPGMTNQDNK IWKNATKSNVNNAVNTLVERWNEKYAQAYPNVSAKIDYDDEMAYSESQLIAKFGTAFKAVNNSLNVNFGAISEG KMQEEVISFKQIYYNVNVNEPTRPSRFFGKAVTKEQLQALGVNAENPPAYISSVAYGRQVYLKLSTNSHSTKVKA AFDAAVSGKSVSGDVELTNIIKNSSFKAVIYGGSAKDEVQIIDGNLGDLRDILKKGATFNRETPGVPIAYTTNFL KDNELAVIKNNSEYIETTSKAYTDGKINIDHSGGYVAQFNISWDEVNYDPEGNEIVQHKNWSENNKSKLAHFTSS IYLPGNARNINVYAKECTGLAWEWWRTVIDDRNLPLVKNRNISIWGTTLYPKYSNKVDNPIE streptolysin O (Streptococcus pyogenes) BAB41212.2 GI : 71061060 ( SEQ ID NO: 3)

MSNKKTFKKYSRVAGLLTAALIIGNLVTANAESNKQNTASTETTTTSEQPKPESSELTIEKAGQKMDDM LNSNDMIKLAPKEMPLESAEKEEKKSEDKKKSEEDHTEEINDKIYSLNYNELEVLAKNGETIENFVPKEGVKKAD KFIVIERKKKNINTTPVDISIIDSVTDRTYPAALQLANKGFTENKPDAWTKRNPQKIHIDLPGMGDKATVEVND PTYANVSTAIDNLVNQWHDNYSGGNTLPARTQYTESMVYSKSQIEAALNVNSKILDGTLGIDFKSISKGEKKVMI AAYKQIFYTVSANLPNNPADVFDKSVTFKDLQRKGVSNEAPPLFVSNVAYGRTVFVKLETSSKSNDVEAAFSAAL KGTDVKTNGKYSDILENSSFTAWLGGDAAEHNKWTKDFDVIRNVIKDNATFSRKNPAYPISYTSVFLKNNKIA GVNNRTEYVETTSTEYTSGKINLSHQGAYVAQYEILWDEINYDDKGKEVITKRRWDNNWYSKTSPFSTVIPLGAN SRNIRIMARECTGLAWEWWRKVIDERDVKLSKEINVNISGSTLSPYGSITYK perf ringolysin O (Clostridium perfringens) NP_561079.1

GI : 18309145 (SEQ ID NO: 4)

MIRFKKTKLIASIAMALCLFSQPVISFSKDITDKNQSIDSGISSLSYNRNEVLASNGDKIESFVPKEGK KTGNKFIWERQKRSLTTSPVDISIIDSVNDRTYPGALQLADKAFVENRPTILMVKRKPININIDLPGLKGENSI KVDDPTYGKVSGAIDELVSKWNEKYSSTHTLPARTQYSESMVYSKSQISSALNVNAKVLENSLGVDFNAVANNEK KVMILAYKQIFYTVSADLPKNPSDLFDDSVTFNDLKQKGVSNEAPPLMVSNVAYGRTIYVKLETTSSSKDVQAAF KALI KNTDIKNSQQYKDI YENS SFTAWLGGDAQEHNKWTKDFDEIRKVIKDNATFSTKNPAYPISYTSVFLKD NSVAAVHNKTDYIETTSTEYSKGKINLDHSGAYVAQFEVAWDEVSYDKEGNEVLTHKTWDGNYQDKTAHYSTVIP LEANARNIRIKARECTGLAWEWWRDVISEYDVPLTNNINVSIWGTTLYPGSSITYN Pneumolysin ( Streptococcus pneumoniae) NP_359331.1 GI: 933687 (SEQ ID

NO: 5)

MANKAVNDFILAMNYDKKKLLTHQGESIENRFIKEGNQLPDEFWIERKKRSLSTNTSDISVTATNDSR LYPGALLWDETLLENNPTLLAVDRAPMTYSIDLPGLASSDSFLQVEDPSNSSVRGAVNDLLAKWHQDYGQVNNV PARMQYEKITAHSMEQLKVKFGSDFEKTGNSLDIDFNSVHSGEKQIQIVNFKQIYYTVSVDAVKNPGDVFQDTVT VEDLKQRGISAERPLVYISSVAYGRQVYLKLETTSKSDEVEAAFEALIKGVKVAPQTEWKQILDNTEVKAVILGG DPSSGARWTGKVDMVEDLIQEGSRFTADHPGLPISYTTSFLRDNWATFQNSTDYVETKVTAYRNGDLLLDHSG AYVAQYYITWDELSYDHQGKEVLTPKAWDRNGQDLTAHFTTSIPLKGNVRNLSVKIRECTGLAWEWWRTVYEKTD LPLVRKRT I S IWGTTLYPQVEDKVEND decapentaplegic homolog 4, NP_005350.1 (SEQ ID NO: 8)

1 mdnmsitntp tsndaclsiv hslmchrqgg esetfakrai eslvkklkek kdeldslita

61 ittngahpsk cvtiqrtldg rlqvagrkgf phviyarlwr wpdlhknelk hvkycqyafd

121 Ikcdsvcvnp yhyervvspg idlsgltlqs napssmmvkd eyvhdfegqp slsteghsiq

181 tiqhppsnra stetystpal lapsesnats tanfpnipva stsqpasilg gshsegllqi

241 asgpqpgqqq ngftgqpaty hhnstttwtg srtapytpnl phhqnghlqh hppmpphpgh

301 ywpvhnelaf qppisnhpap eywcsiayfe mdvqvgetfk vpsscpivtv dgyvdpsggd

361 rfclgqlsnv hrteaierar Ihigkgvqle ckgegdvwvr clsdhavfvq syyldreagr

421 apgdavhkiy psayikvfdl rqchrqmqqq aataqaaaaa qaaavagnip gpgsvggiap

481 aislsaaagi gvddlrrlci Irmsfvkgwg pdyprqsike tpcwieihlh ralqlldevl

541 htmpiadpqp Id

Cadherin 3, isoform 1 preproprotein, NP_001784.2 (SEQ ID NO: 9)

1 mglprgplas llllqvcwlq caasepcrav freaevtlea ggaeqepgqa Igkvfmgcpg 61 qepalfstdn ddftvrnget vqerrslker nplkifpskr ilrrhkrdwv vapisvpeng

121 kgpfpqrlnq Iksnkdrdtk ifysitgpga dsppegvfav eketgwllln kpldreeiak

181 yelfghavse ngasvedpmn isiivtdqnd hkpkftqdtf rgsvlegvlp gtsvmqvtat

241 deddaiytyn gvvaysihsq epkdphdlmf tihrstgtis vissgldrek vpeytltiqa

301 tdmdgdgstt tavavveild andnapmfdp qkyeahvpen avghevqrlt vtdldapnsp

361 awratylimg gddgdhftit thpesnqgil ttrkgldfea knqhtlyvev tneapfvlkl

421 ptstativvh vedvneapvf vppskvvevq egiptgepvc vytaedpdke nqkisyrilr

481 dpagwlamdp dsgqvtavgt Idredeqfvr nniyevmvla mdngsppttg tgtllltlid

541 vndhgpvpep rqiticnqsp vrqvlnitdk dlsphtspfq aqltddsdiy wtaevneegd

601 tvvlslkkfl kqdtydvhls Isdhgnkeql tviratvcdc hghvetcpgp wkggfilpvl

661 gavlallfll Ivllllvrkk rkikeplllp eddtrdnvfy ygeegggeed qdyditqlhr

721 glearpevvl rndvaptiip tpmyrprpan pdeignfiie nlkaantdpt appydtllvf

781 dyegsgsdaa slssltssas dqdqdydyln ewgsrfkkla dmygggedd

Cadherin 3, isoform 2 precursor, NP_001304124.1 (SEQ ID NO: 10)

1 mglprgplas llllqvcwlq caasepcrav freaevtlea ggaeqepgqa Igkvfmgcpg

61 qepalfstdn ddftvrnget vqerrslker nplkifpskr ilrrhkrdwv vapisvpeng

121 kgpfpqrlnq Iksnkdrdtk ifysitgpga dsppegvfav eketgwllln kpldreeiak

181 yelfghavse ngasvedpmn isiivtdqnd hkpkftqdtf rgsvlegvlp gtsvmqvtat

241 deddaiytyn gvvaysihsq epkdphdlmf tihrstgtis vissgldrek vpeytltiqa

301 tdmdgdgstt tavavveild andnapmfdp qkyeahvpen avghevqrlt vtdldapnsp

361 awratylimg gddgdhftit thpesnqgil ttrkgldfea knqhtlyvev tneapfvlkl

421 ptstativvh vedvneapvf vppskvvevq egiptgepvc vytaedpdke nqkisyrilr

481 dpagwlamdp dsgqvtavgt Idredeqfvr nniyevmvla mdngsppttg tgtllltlid

541 vndhgpvpep rqiticnqsp vrqvlnitdk dlsphtspfq aqltddsdiy wtaevneegd

601 tvvlslkkfl kqdtydvhls Isdhgnkeql tviratvcdc hghvetcpgp wkggfilpvl

661 gavlallfll Ivllllvrkk rkikeplllp eddtrdnvfy ygeegggeed qdyditqlhr

721 glearpevvl rndvaptiip tpmyrprpan pdeignfiie grgergsqrg ngglqlargr

781 trrs

Cadherin 3, isoform 3, NP_001304125.1 (SEQ ID NO: 11)

1 mgcpgqepal fstdnddftv rngetvqerr slkernplki fpskrilrrh krdwvvapis

61 vpengkgpfp qrlnqlksnk drdtkifysi tgpgadsppe gvfaveketg wlllnkpldr

121 eeiakyelfg havsengasv edpmnisiiv tdqndhkpkf tqdtfrgsvl egvlpgtsvm

181 qvtatdedda iytyngvvay sihsqepkdp hdlmftihrs tgtisvissg Idrekvpeyt

241 Itiqatdmdg dgstttavav veildandna pmfdpqkyea hvpenavghe vqrltvtdld

301 apnspawrat ylimggddgd hftitthpes nqgilttrkg Idfeaknqht lyvevtneap

361 fvlklptsta tivvhvedvn eapvfvppsk vvevqegipt gepvcvytae dpdkenqkis

421 yrilrdpagw lamdpdsgqv tavgtldred eqfvrnniye vmvlamdngs ppttgtgtll

481 Itlidvndhg pvpeprqiti cnqspvrqvl nitdkdlsph tspfqaqltd dsdiywtaev

541 neegdtvvls Ikkflkqdty dvhlslsdhg nkeqltvira tvcdchghve tcpgpwkggf

601 ilpvlgavla llflllvlll Ivrkkrkike plllpeddtr dnvfyygeeg ggeedqdydi

661 tqlhrglear pevvlrndva ptiiptpmyr prpanpdeig nfiienlkaa ntdptappyd

721 tllvfdyegs gsdaaslssl tssasdqdqd ydylnewgsr fkkladmygg gedd

Chorionic gonadotropin beta subunit 3, precursor, NP_000728.1 (SEQ ID NO:

12)

1 memfqgllll lllsmggtwa skeplrprcr pinatlavek egcpvcitvn tticagycpt 61 mtrvlqgvlp alpqvvcnyr dvrfesirlp gcprgvnpvv syavalscqc alcrrsttdc 121 ggpkdhpltc ddprfqdsss skapppslps psrlpgpsdt pilpq

Chorionic gonadotropin beta subunit 5, precursor, NP_149032.1 (SEQ ID NO:

13)

Cytochrome c oxidase assembly factor 1 homolog, isoform a, NP_001308126.1 , NP_001308127.1, NP_001308128.1, NP_001308129.1 , NP_001337853.1, NP_001337854.1, NP_001337855.1 , NP_001337856.1 , NP_060694.2 (SEQ ID NO: 14)

1 mmwqkyagsr rsmplgaril fhgvfyaggf aivyyliqkf hsralyykla veqlqshpea

61 qealgpplni hylklidren fvdivdaklk ipvsgskseg llyvhssrgg pfqrwhldev

121 flelkdgqqi pvfklsgeng devkke

Cytochrome c oxidase assembly factor 1 homolog, isoform b, NP_001308130.1 (SEQ ID NO: 15)

1 mplgarilfh gvfyaggfai vyyliqkfhs ralyyklave qlqshpeaqe algpplnihy 61 Iklidrenfv divdaklkip vsgsksegll yvhssrggpf qrwhldevfl elkdgqqipv 121 fklsgengde vkke

Cytochrome c oxidase assembly factor 1 homolog, isoform c, NP_001308131.1 , NP_001308132.1 , NP_001308133.1 , NP_001308134.1 (SEQ ID NO: 16?

1 mmwqkyagsr rsmplgaril fhgvfyaggf aivyyliqsk ypasrlrpdl llacscssir 61 gnt

Cytochrome c oxidase assembly factor 1 homolog, isoform d, NP_001337857.1 (SEQ ID NO: 17)

1 mqeaggqclw eqgsfstvcs mpgalplcit sfkfhsraly yklaveqlqs hpeaqealgp 61 plnihylkli drenfvdivd aklkipvsgs ksegllyvhs srggpfqrwh Idevflelkd 121 gqqipvfkls gengdevkke

Estrogen receptor binding site associated, antigen, 9, NP_001265867.1 , NP_004206.1, NP_936056.1, NP_001308129.1 , (SEQ ID NO: 18)

1 maitqfrlfk fctclatvfs flkrlicrsg rgrklsgdqi tlpttvdyss vpkqtdveew

61 tswdedapts vkieggngnv atqqnsleql epdyfkdmtp tirktqkivi kkreplnfgi

121 pdgstgfssr laatqdlpfi hqsselgdld twqentnawe eeedaawqae evlrqqklad

181 rekraaeqqr kkmekeaqrl mkkeqnkigv kls

ETS transcription factor, isoform a, NP_001964.2 (SEQ ID NO: 19)

1 mdsaitlwqf llqllqkpqn khmicwtsnd gqfkllqaee varlwgirkn kpnmnydkls

61 ralryyyvkn iikkvngqkf vykfvsypei Inmdpmtvgr iegdceslnf sevsssskdv

121 enggkdkppq pgaktssrnd yihsglyssf tlnslnssnv klfklikten paeklaekks

181 pqeptpsvik fvttpskkpp vepvaatisi gpsispssee tiqaletlvs pklpsleapt

241 sasnvmtafa ttppissipp Iqepprtpsp plsshpdidt didsvasqpm elpenlslep

301 kdqdsvllek dkvnnssrsk kpkglelapt Ivitssdpsp Igilspslpt asltpaffsq

361 tpiiltpspl Issihfwstl spvaplspar Iqgantlfqf psvlnshgpf tlsgldgpst

421 pgpfspdlqk t

ETS transcription factor, isoform b, NP_068567.1 (SEQ ID NO: 20)

1 mdsaitlwqf llqllqkpqn khmicwtsnd gqfkllqaee varlwgirkn kpnmnydkls

61 ralryyyvkn iikkvngqkf vykfvsypei Inmdpmtvgr iegdceslnf sevsssskdv

121 enggkdkppq pgaktssrnd yihsglyssf tlnslnssnv klfklikten paeklaekks

181 pqeptpsvik fvttpskkpp vepvaatisi gpsispssee tiqaletlvs pklpsleapt

241 sasnvmtafa ttppissipp Iqepprtpsp plsshpdidt didsvasqpm elpenlslep

301 kdqdsvllek dkvnnssrsk kpkglelapt Ivitssdpsp Igilspslpt asltpaffsq

361 vacslfmvsp llsficpfkq iqnlytqvcf lllrfvlerl cvtvm

Receptor tyrosine-protein kinase erbB-2, isoform a precursor, NP_004439.2 (SEQ ID NO: 21)

1 melaalcrwg lllallppga astqvctgtd mklrlpaspe thldmlrhly qgcqvvqgnl

61 eltylptnas Isflqdiqev qgyvliahnq vrqvplqrlr ivrgtqlfed nyalavldng

121 dplnnttpvt gaspgglrel qlrslteilk ggvliqrnpq Icyqdtilwk difhknnqla

181 Itlidtnrsr achpcspmck gsrcwgesse dcqsltrtvc aggcarckgp Iptdccheqc

241 aagctgpkhs dclaclhfnh sgicelhcpa Ivtyntdtfe smpnpegryt fgascvtacp

301 ynylstdvgs ctlvcplhnq evtaedgtqr cekcskpcar vcyglgmehl revravtsan

361 iqefagckki fgslaflpes fdgdpasnta plqpeqlqvf etleeitgyl yisawpdslp

421 dlsvfqnlqv irgrilhnga ysltlqglgi swlglrslre Igsglalihh nthlcfvhtv

481 pwdqlfrnph qallhtanrp edecvgegla chqlcarghc wgpgptqcvn csqflrgqec

541 veecrvlqgl preyvnarhc Ipchpecqpq ngsvtcfgpe adqcvacahy kdppfcvarc

601 psgvkpdlsy mpiwkfpdee gacqpcpinc thscvdlddk gcpaeqrasp Itsiisavvg

661 illvvvlgvv fgilikrrqq kirkytmrrl Iqetelvepl tpsgampnqa qmrilketel

721 rkvkvlgsga fgtvykgiwi pdgenvkipv aikvlrents pkankeilde ayvmagvgsp

781 yvsrllgicl tstvqlvtql mpygclldhv renrgrlgsq dllnwcmqia kgmsyledvr

841 Ivhrdlaarn vlvkspnhvk itdfglarll dideteyhad ggkvpikwma lesilrrrft

901 hqsdvwsygv tvwelmtfga kpydgipare ipdllekger Ipqppictid vymimvkcwm

961 idsecrprfr elvsefsrma rdpqrfvviq nedlgpaspl dstfyrslle dddmgdlvda

1021 eeylvpqqgf fcpdpapgag gmvhhrhrss strsgggdlt Iglepseeea prsplapseg

1081 agsdvfdgdl gmgaakglqs Ipthdpsplq rysedptvpl psetdgyvap Itcspqpeyv

1141 nqpdvrpqpp spregplpaa rpagatlerp ktlspgkngv vkdvfafgga venpeyltpq

1201 ggaapqphpp pafspafdnl yywdqdpper gappstfkgt ptaenpeylg Idvpv

Receptor tyrosine-protein kinase erbB-2, isoform b, NP_001005862.1 (SEQ ID NO: 22)

1 mklrlpaspe thldmlrhly qgcqvvqgnl eltylptnas Isflqdiqev qgyvliahnq 61 vrqvplqrlr ivrgtqlfed nyalavldng dplnnttpvt gaspgglrel qlrslteilk 121 ggvliqrnpq Icyqdtilwk difhknnqla Itlidtnrsr achpcspmck gsrcwgesse

181 dcqsltrtvc aggcarckgp Iptdccheqc aagctgpkhs dclaclhfnh sgicelhcpa

241 Ivtyntdtfe smpnpegryt fgascvtacp ynylstdvgs ctlvcplhnq evtaedgtqr

301 cekcskpcar vcyglgmehl revravtsan iqefagckki fgslaflpes fdgdpasnta

361 plqpeqlqvf etleeitgyl yisawpdslp dlsvfqnlqv irgrilhnga ysltlqglgi

421 swlglrslre Igsglalihh nthlcfvhtv pwdqlfrnph qallhtanrp edecvgegla

481 chqlcarghc wgpgptqcvn csqflrgqec veecrvlqgl preyvnarhc Ipchpecqpq

541 ngsvtcfgpe adqcvacahy kdppfcvarc psgvkpdlsy mpiwkfpdee gacqpcpinc

601 thscvdlddk gcpaeqrasp Itsiisavvg illvvvlgvv fgilikrrqq kirkytmrrl

661 Iqetelvepl tpsgampnqa qmrilketel rkvkvlgsga fgtvykgiwi pdgenvkipv

721 aikvlrents pkankeilde ayvmagvgsp yvsrllgicl tstvqlvtql mpygclldhv

781 renrgrlgsq dllnwcmqia kgmsyledvr Ivhrdlaarn vlvkspnhvk itdfglarll

841 dideteyhad ggkvpikwma lesilrrrft hqsdvwsygv tvwelmtfga kpydgipare

901 ipdllekger Ipqppictid vymimvkcwm idsecrprfr elvsefsrma rdpqrfvviq

961 nedlgpaspl dstfyrslle dddmgdlvda eeylvpqqgf fcpdpapgag gmvhhrhrss

1021 strsgggdlt Iglepseeea prsplapseg agsdvfdgdl gmgaakglqs Ipthdpsplq

1081 rysedptvpl psetdgyvap Itcspqpeyv nqpdvrpqpp spregplpaa rpagatlerp

1141 ktlspgkngv vkdvfafgga venpeyltpq ggaapqphpp pafspafdnl yywdqdpper

1201 gappstfkgt ptaenpeylg Idvpv

Receptor tyrosine-protein kinase erbB-2, isoform c, NP_001276865.1 (SEQ ID NO: 23)

1 mprgswkpqv ctgtdmklrl paspethldm Irhlyqgcqv vqgnleltyl ptnaslsflq

61 diqevqgyvl iahnqvrqvp Iqrlrivrgt qlfednyala vldngdplnn ttpvtgaspg

121 glrelqlrsl teilkggvli qrnpqlcyqd tilwkdifhk nnqlaltlid tnrsrachpc

181 spmckgsrcw gessedcqsl trtvcaggca rckgplptdc cheqcaagct gpkhsdclac

241 Ihfnhsgice Ihcpalvtyn tdtfesmpnp egrytfgasc vtacpynyls tdvgsctlvc

301 plhnqevtae dgtqrcekcs kpcarvcygl gmehlrevra vtsaniqefa gckkifgsla

361 flpesfdgdp asntaplqpe qlqvfetlee itgylyisaw pdslpdlsvf qnlqvirgri

421 Ihngaysltl qglgiswlgl rslrelgsgl alihhnthlc fvhtvpwdql frnphqallh

481 tanrpedecv geglachqlc arghcwgpgp tqcvncsqfl rgqecveecr vlqglpreyv

541 narhclpchp ecqpqngsvt cfgpeadqcv acahykdppf cvarcpsgvk pdlsympiwk

601 fpdeegacqp cpincthscv dlddkgcpae qraspltsii savvgillvv vlgvvfgili

661 krrqqkirky tmrrllqete Ivepltpsga mpnqaqmril ketelrkvkv Igsgafgtvy

721 kgiwipdgen vkipvaikvl rentspkank eildeayvma gvgspyvsrl Igicltstvq

781 Ivtqlmpygc lldhvrenrg rlgsqdllnw cmqiakgmsy ledvrlvhrd laarnvlvks

841 pnhvkitdfg larlldidet eyhadggkvp ikwmalesil rrrfthqsdv wsygvtvwel

901 mtfgakpydg ipareipdll ekgerlpqpp ictidvymim vkcwmidsec rprfrelvse

961 fsrmardpqr fvviqnedlg paspldstfy rslledddmg dlvdaeeylv pqqgffcpdp

1021 apgaggmvhh rhrssstrsg ggdltlglep seeeaprspl apsegagsdv fdgdlgmgaa

1081 kglqslpthd psplqrysed ptvplpsetd gyvapltcsp qpeyvnqpdv rpqppspreg

1141 plpaarpaga tlerpktlsp gkngvvkdvf afggavenpe yltpqggaap qphpppafsp

1201 afdnlyywdq dppergapps tfkgtptaen peylgldvpv

Receptor tyrosine-protein kinase erbB-2, isoform d precursor,

NP_001276866.1 (SEQ ID NO: 24)

1 melaalcrwg lllallppga astqvctgtd mklrlpaspe thldmlrhly qgcqvvqgnl

61 eltylptnas Isflqdiqev qgyvliahnq vrqvplqrlr ivrgtqlfed nyalavldng

121 dplnnttpvt gaspgglrel qlrslteilk ggvliqrnpq Icyqdtilwk difhknnqla

181 Itlidtnrsr achpcspmck gsrcwgesse dcqsltrtvc aggcarckgp Iptdccheqc

241 aagctgpkhs dclaclhfnh sgicelhcpa Ivtyntdtfe smpnpegryt fgascvtacp

301 ynylstdvgs ctlvcplhnq evtaedgtqr cekcskpcar vcyglgmehl revravtsan

361 iqefagckki fgslaflpes fdgdpasnta plqpeqlqvf etleeitgyl yisawpdslp

421 dlsvfqnlqv irgrilhnga ysltlqglgi swlglrslre Igsglalihh nthlcfvhtv

481 pwdqlfrnph qallhtanrp edecvgegla chqlcarghc wgpgptqcvn csqflrgqec

541 veecrvlqgl preyvnarhc Ipchpecqpq ngsvtcfgpe adqcvacahy kdppfcvarc

601 psgvkpdlsy mpiwkfpdee gacqpcpinc thscvdlddk gcpaeqrasp Itsiisavvg

661 illvvvlgvv fgilikrrqq kirkytmrrl Iqetelvepl tpsgampnqa qmrilketel

721 rkvkvlgsga fgtvykgiwi pdgenvkipv aikvlrents pkankeilde ayvmagvgsp

781 yvsrllgicl tstvqlvtql mpygclldhv renrgrlgsq dllnwcmqia kgmsyledvr

841 Ivhrdlaarn vlvkspnhvk itdfglarll dideteyhad ggkvpikwma lesilrrrft

901 hqsdvwsygv tvwelmtfga kpydgipare ipdllekger Ipqppictid vymimvkcwm

961 idsecrprfr elvsefsrma rdpqrfvviq nedlgpaspl dstfyrslle dddmgdlvda 1021 eeylvpqqgf fcpdpapgag gmvhhrhrss strnm Receptor tyrosine-protein kinase erbB-2, isoform e, NP_001276867.1 (SEQ ID NO: 25)

1 mklrlpaspe thldmlrhly qgcqvvqgnl eltylptnas Isflqdiqev qgyvliahnq

61 vrqvplqrlr ivrgtqlfed nyalavldng dplnnttpvt gaspgglrel qlrslteilk

121 ggvliqrnpq Icyqdtilwk difhknnqla Itlidtnrsr achpcspmck gsrcwgesse

181 dcqsltrtvc aggcarckgp Iptdccheqc aagctgpkhs dclaclhfnh sgicelhcpa

241 Ivtyntdtfe smpnpegryt fgascvtacp ynylstdvgs ctlvcplhnq evtaedgtqr

301 cekcskpcar vcyglgmehl revravtsan iqefagckki fgslaflpes fdgdpasnta

361 plqpeqlqvf etleeitgyl yisawpdslp dlsvfqnlqv irgrilhnga ysltlqglgi

421 swlglrslre Igsglalihh nthlcfvhtv pwdqlfrnph qallhtanrp edecvgegla

481 chqlcarghc wgpgptqcvn csqflrgqec veecrvlqgl preyvnarhc Ipchpecqpq

541 ngsvtcfgpe adqcvacahy kdppfcvarc psgvkpdlsy mpiwkfpdee gacqpcpinc

601 ths

Inosine monophosphate dehydrogenase 2 , NP_000875.2 (SEQ ID NO: 26)

1 madylisggt syvpddglta qqlfncgdgl tyndflilpg yidftadqvd Itsaltkkit

61 Iktplvsspm dtvteagmai amaltggigf ihhnctpefq anevrkvkky eqgfitdpvv

121 Ispkdrvrdv feakarhgfc gipitdtgrm gsrlvgiiss rdidflkeee hdcfleeimt

181 kredlvvapa gitlkeanei Iqrskkgklp ivneddelva iiartdlkkn rdyplaskda

241 kkqllcgaai gtheddkyrl dllaqagvdv vvldssqgns ifqinmikyi kdkypnlqvi

301 ggnvvtaaqa knlidagvda Irvgmgsgsi citqevlacg rpqatavykv seyarrfgvp

361 viadggiqnv ghiakalalg astvmmgsll aatteapgey ffsdgirlkk yrgmgsldam

421 dkhlssqnry fseadkikva qgvsgavqdk gsihkfvpyl iagiqhscqd igaksltqvr

481 ammysgelkf ekrtssaqve ggvhslhsye krlf

KRAS proto-oncogene, GTPase, isoform a, NP_203524.1 (SEQ ID NO: 27)

1 mteyklvvvg aggvgksalt iqliqnhfvd eydptiedsy rkqvvidget clldildtag

61 qeeysamrdq ymrtgegflc vfainntksf edihhyreqi krvkdsedvp mvlvgnkcdl

121 psrtvdtkqa qdlarsygip fietsaktrq rvedafytlv reirqyrlkk iskeektpgc

181 vkikkciim

KRAS proto-oncogene, GTPase, isoform b, NP_004976.2 (SEQ ID NO: 28)

1 mteyklvvvg aggvgksalt iqliqnhfvd eydptiedsy rkqvvidget clldildtag

61 qeeysamrdq ymrtgegflc vfainntksf edihhyreqi krvkdsedvp mvlvgnkcdl

121 psrtvdtkqa qdlarsygip fietsaktrq gvddafytlv reirkhkekm skdgkkkkkk

181 sktkcvim Transforming growth factor beta receptor 2, isoform A precursor, NP_001020018.1 (SEQ ID NO: 29)

1 mgrgllrglw plhivlwtri astipphvqk sdvemeaqkd eiicpscnrt ahplrhinnd

61 mivtdnngav kfpqlckfcd vrfstcdnqk scmsncsits icekpqevcv avwrkndeni

121 tletvchdpk Ipyhdfiled aaspkcimke kkkpgetffm cscssdecnd niifseeynt

181 snpdlllvif qvtgisllpp Igvaisviii fycyrvnrqq klsstwetgk trklmefseh

241 caiileddrs disstcanni nhntellpie Idtlvgkgrf aevykaklkq ntseqfetva

301 vkifpyeeya swktekdifs dinlkhenil qfltaeerkt elgkqywlit afhakgnlqe

361 yltrhviswe dlrklgssla rgiahlhsdh tpcgrpkmpi vhrdlkssni Ivkndltccl

421 cdfglslrld ptlsvddlan sgqvgtarym apevlesrmn lenvesfkqt dvysmalvlw

481 emtsrcnavg evkdyeppfg skvrehpcve smkdnvlrdr grpeipsfwl nhqgiqmvce

541 tltecwdhdp earltaqcva erfselehld rlsgrscsee kipedgslnt tk

Transforming growth factor beta receptor 2, isoform B precursor, NP_003233.4 (SEQ ID NO: 30)

1 mgrgllrglw plhivlwtri astipphvqk svnndmivtd nngavkfpql ckfcdvrfst

61 cdnqkscmsn csitsicekp qevcvavwrk ndenitletv chdpklpyhd filedaaspk

121 cimkekkkpg etffmcscss decndniifs eeyntsnpdl llvifqvtgi sllpplgvai

181 sviiifycyr vnrqqklsst wetgktrklm efsehcaiil eddrsdisst canninhnte

241 llpieldtlv gkgrfaevyk aklkqntseq fetvavkifp yeeyaswkte kdifsdinlk

301 henilqflta eerktelgkq ywlitafhak gnlqeyltrh viswedlrkl gsslargiah

361 Ihsdhtpcgr pkmpivhrdl kssnilvknd Itcclcdfgl slrldptlsv ddlansgqvg

421 tarymapevl esrmnlenve sfkqtdvysm alvlwemtsr cnavgevkdy eppfgskvre

481 hpcvesmkdn vlrdrgrpei psfwlnhqgi qmvcetltec wdhdpearlt aqcvaerfse

541 lehldrlsgr scseekiped gslnttk

Actinin alpha 4, isoform 1, NP_004915.2 (SEQ ID NO: 31)

1 mvdyhaanqs yqygpssagn gaggggsmgd ymaqeddwdr dllldpawek qqrktftawc

61 nshlrkagtq ienidedfrd glklmlllev isgerlpkpe rgkmrvhkin nvnkaldfia 121 skgvklvsig aeeivdgnak mtlgmiwtii Irfaiqdisv eetsakegll Iwcqrktapy

181 knvnvqnfhi swkdglafna lihrhrpeli eydklrkddp vtnlnnafev aekyldipkm

241 Idaedivnta rpdekaimty vssfyhafsg aqkaetaanr ickvlavnqe nehlmedyek

301 lasdllewir rtipwledrv pqktiqemqq kledfrdyrr vhkppkvqek cqleinfntl

361 qtklrlsnrp afmpsegkmv sdinngwqhl eqaekgyeew llneirrler Idhlaekfrq

421 kasiheawtd gkeamlkhrd yetatlsdik alirkheafe sdlaahqdrv eqiaaiaqel

481 neldyydshn vntrcqkicd qwdalgslth srrealekte kqleaidqlh leyakraapf

541 nnwmesamed Iqdmfivhti eeieglisah dqfkstlpda drereailai hkeaqriaes

601 nhiklsgsnp yttvtpqiin skwekvqqlv pkrdhallee qskqqsnehl rrqfasqanv

661 vgpwiqtkme eigrisiemn gtledqlshl kqyersivdy kpnldlleqq hqliqealif

721 dnkhtnytme hirvgweqll ttiartinev enqiltrdak gisqeqmqef rasfnhfdkd

781 hggalgpeef kaclislgyd vendrqgeae fnrimslvdp nhsglvtfqa fidfmsrett

841 dtdtadqvia sfkvlagdkn fitaeelrre Ippdqaeyci armapyqgpd avpgaldyks

901 fstalygesd 1

Actinin alpha 4, isoform 2, NP_001308962.1 (SEQ ID NO: 32)

1 mvdyhaanqs yqygpssagn gaggggsmgd ymaqeddwdr dllldpawek qqrktftawc

61 nshlrkagtq ienidedfrd glklmlllev isgerlpkpe rgkmrvhkin nvnkaldfia

121 skgvklvsig aeeivdgnak mtlgmiwtii Irfaiqdisv eetsakegll Iwcqrktapy

181 knvnvqnfhi swkdglafna lihrhrpeli eydklrkddp vtnlnnafev aekyldipkm

241 Idaedivgtl rpdekaimty vscfyhafsg aqkaetaanr ickvlavnqe nehlmedyek

301 lasdllewir rtipwledrv pqktiqemqq kledfrdyrr vhkppkvqek cqleinfntl

361 qtklrlsnrp afmpsegkmv sdinngwqhl eqaekgyeew llneirrler Idhlaekfrq

421 kasiheawtd gkeamlkhrd yetatlsdik alirkheafe sdlaahqdrv eqiaaiaqel

481 neldyydshn vntrcqkicd qwdalgslth srrealekte kqleaidqlh leyakraapf

541 nnwmesamed Iqdmfivhti eeieglisah dqfkstlpda drereailai hkeaqriaes

601 nhiklsgsnp yttvtpqiin skwekvqqlv pkrdhallee qskqqsnehl rrqfasqanv

661 vgpwiqtkme eigrisiemn gtledqlshl kqyersivdy kpnldlleqq hqliqealif

721 dnkhtnytme hirvgweqll ttiartinev enqiltrdak gisqeqmqef rasfnhfdkk

781 qtgsmdsddf rallistgys Igeaefnrim slvdpnhsgl vtfqafidfm srettdtdta

841 dqviasfkvl agdknfitae elrrelppdq aeyciarmap yqgpdavpga Idyksfstal

901 ygesdl

Activin A receptor type 1, NP_001096.1, NP_001104537.1, NP_001334592.1, NP_001334593.1 , NP_001334594.1, NP_001334595.1 , NP_001334596.1 (SEQ ID NO: 33)

1 mvdgvmilpv limialpsps medekpkvnp klymcvcegl scgnedhceg qqcfsslsin

61 dgfhvyqkgc fqvyeqgkmt cktppspgqa veccqgdwcn rnitaqlptk gksfpgtqnf

121 hlevgliils vvfavcllac llgvalrkfk rrnqerlnpr dveygtiegl ittnvgdstl

181 adlldhscts gsgsglpflv qrtvarqitl lecvgkgryg evwrgswqge nvavkifssr

241 dekswfrete lyntvmlrhe nilgfiasdm tsrhsstqlw lithyhemgs lydylqlttl

301 dtvsclrivl siasglahlh ieifgtqgkp aiahrdlksk nilvkkngqc ciadlglavm

361 hsqstnqldv gnnprvgtkr ymapevldet iqvdcfdsyk rvdiwafglv Iwevarrmvs

421 ngivedykpp fydvvpndps fedmrkvvcv dqqrpnipnr wfsdptltsl aklmkecwyq

481 npsarltalr ikktltkidn sldklktdc

Alcohol dehydrogenase 10 (class I) , gamma polypeptide, NP_000660.1 (SEQ ID NO: 34)

1 mstagkvikc kaavlwelkk pfsieeveva ppkahevrik mvaagicrsd ehvvsgnlvt

61 plpvilghea agivesvgeg vttvkpgdkv iplftpqcgk cricknpesn yclkndlgnp

121 rgtlqdgtrr ftcsgkpihh fvgvstfsqy tvvdenavak idaasplekv cligcgfstg

181 ygsavkvakv tpgstcavfg Iggvglsvvm gckaagaari iavdinkdkf akakelgate

241 cinpqdykkp iqevlkemtd ggvdfsfevi grldtmmasl Iccheacgts vivgvppdsq

301 nlsinpmlll tgrtwkgaif ggfkskesvp klvadfmakk fsldalitni Ipfekinegf

361 dllrsgksir tvltf

Adenosine A2a receptor, NP_000666.2, NP_001265426.1 , NP_001265427.1 , NP_001265428.1, NP_001265429.1 (SEQ ID NO: 35)

1 mpimgssvyi tvelaiavla ilgnvlvcwa vwlnsnlqnv tnyfvvslaa adiavgvlai

61 pfaitistgf caachgclfi acfvlvltqs sifsllaiai dryiairipl rynglvtgtr

121 akgiiaicwv Isfaigltpm Igwnncgqpk egknhsqgcg egqvaclfed vvpmnymvyf

181 nffacvlvpl llmlgvylri flaarrqlkq mesqplpger arstlqkevh aakslaiivg

241 Ifalcwlplh iincftffcp dcshaplwlm ylaivlshtn svvnpfiyay rirefrqtfr

301 kiirshvlrq qepfkaagts arvlaahgsd geqvslrlng hppgvwangs aphperrpng

361 yalglvsggs aqesqgntgl pdvellshel kgvcpeppgl ddplaqdgag vs Rho guanine nucleotide exchange factor 16, NP_055263.2 (SEQ ID NO: 36)

1 maqrhsdssl eekllghrfh selrldaggn pasglpmvrg sprvrddaaf qpqvpappqp

61 rppgheepwp ivlstespaa Iklgtqqlip kslavaskak tparhqsfga avlsreaarr

121 dpkllpapsf slddmdvdkd pggmlrrnlr nqsyraamkg Igkpggqgda iqlspklqal

181 aeepsqphtr spaknkktlg rkrghkgsfk ddpqlyqeiq erglntsqes dddildesss

241 pegtqkvdat ivvksyrpaq vtwsqlpevv elgildqlst eerkrqeamf eiltsefsyq

301 hslsilveef Iqskelratv tqmehhhlfs nildvlgasq rffedleqrh kaqvlvedis

361 dileehaekh fhpyiaycsn evyqqrtlqk lissnaafre alreierrpa cgglpmlsfl

421 ilpmqrvtrl pllmdtlclk tqghseryka asralkaisk Ivrqcnegah rmermeqmyt

481 Ihtqldfskv kslplisasr wllkrgelfl veetglfrki asrptcylfl fndvlvvtkk

541 kseesymvqd yaqmnhiqve kiepselplp gggnrsssvp hpfqvtllrn segrqeqlll

601 ssdsasdrar wivalthser qwqglsskgd Ipqveitkaf fakqadevtl qqadvvlvlq

661 qedgwlyger Irdgetgwfp edfarfitsr vavegnvrrm erlrvetdv

B-cell linker, isoform 1, NP_037446.1 (SEQ ID NO: 37)

1 mdklnkitvp asqklrqlqk mvhdiknneg gimnkikklk vkappsvprr dyasespade

61 eeqwsddfds dyenpdehsd semyvmpaee naddsyeppp veqetrpvhp alpfargeyi

121 dnrssqrhsp pfsktlpskp swpsekarlt stlpaltalq kpqvppkpkg lledeadyvv

181 pvedndenyi hptesssppp ekapmvnrst kpnsstpasp pgtasgrnsg awetkspppa

241 apsplpragk kpttplkttp vasqqnassv ceekpipaer hrgsshrqea vqspvfppaq

301 kqihqkpipl prfteggnpt vdgplpsfss nstiseqeag vlckpwyaga cdrksaeeal

361 hrsnkdgsfl irkssghdsk qpytlvvffn krvynipvrf ieatkqyalg rkkngeeyfg

421 svaeiirnhq hsplvlidsq nntkdstrlk yavkvs

B-cell linker, isoform 2, NP_001107566.1 (SEQ ID NO: 38)

1 mdklnkitvp asqklrqlqk mvhdiknneg gimnkikklk vkappsvprr dyasespade

61 eeqwsddfds dyenpdehsd semyvmpaee naddsyeppp veqetrpvhp alpfargeyi

121 dnrssqrhsp pfsktlpskp swpsekarlt stlpaltalq kpqvppkpkg lledeadyvv

181 pvedndenyi hptesssppp ekgrnsgawe tkspppaaps plpragkkpt tplkttpvas

241 qqnassvcee kpipaerhrg sshrqeavqs pvfppaqkqi hqkpiplprf teggnptvdg

301 plpsfssnst iseqeagvlc kpwyagacdr ksaeealhrs nkdgsflirk ssghdskqpy

361 tlvvffnkrv ynipvrfiea tkqyalgrkk ngeeyfgsva eiirnhqhsp Ivlidsqnnt

421 kdstrlkyav kvs

B-cell linker, isoform 3, NP_001245369.1 (SEQ ID NO: 39)

1 mdklnkitvp asqklrqlqk mvhdiknneg gimnkikklk vkappsvprr dyasespade

61 eeqwsddfds dyenpdehsd semyvmpaee naddsyeppp veqetrpvhp alpfargeyi

121 dnrssqrhsp pfsktlpskp swpsekarlt stlpaltalq kpqvppkpkg lledeadyvv

181 pvedndenyi hptesssppp ekapmvnrst kpnsstpasp pgtasgrnsg awetkspppa

241 apsplpragk kpttplkttp vasqqnassv ceekpipaer hrgsshrqea vqspvfppaq

301 kqihqkpipl prfteggnpt vdgplpsfss nstiseqeag vlckpwyaga cdrksaeeal

361 hrsnkyfgsv aeiirnhqhs plvlidsqnn tkdstrlkya vkvs

B-cell linker, isoform 4, NP_001245370.1 (SEQ ID NO: 40)

1 mdklnkitvp asqklrqlqk mvhdiknneg gimnkikklk vkappsvprr dyasespade

61 eeqwsddfds dyenpdehsd semyvmpaee naddsyeppp veqetrpvhp alpfargeyi

121 dnrssqrhsp pfsktlpskp swpsekarlt stlpaltalq kpqvppkpkg lledeadyvv

181 pvedndenyi hptesssppp ekgrnsgawe tkspppaaps plpragkkpt tplkttpvas

241 qqnassvcee kpipaerhrg sshrqeavqs pvfppaqkqi hqkpiplprf teggnptvdg

301 plpsfssnst iseqeagvlc kpwyagacdr ksaeealhrs nkyfgsvaei irnhqhsplv

361 lidsqnntkd strlkyavkv s

B-cell linker, isoform 5, NP_001245371.1 (SEQ ID NO: 41)

1 mdklnkitvp asqklrqlqk mvhdiknneg gimnkikklk vkappsvprr dyasespade

61 eeqwsddfds dyenpdehsd semyvmpaee naddsyeppp veqetrpvhp alpfargtas

121 grnsgawetk spppaapspl pragkkpttp Ikttpvasqq nassvceekp ipaerhrgss

181 hrqeavqspv fppaqkqihq kpiplprfte ggnptvdgpl psfssnstis eqeagvlckp

241 wyagacdrks aeealhrsnk yfgsvaeiir nhqhsplvli dsqnntkdst rlkyavkvs

Basonuclin 1, isoform a, NP_001708.3 (SEQ ID NO: 42)

1 mrrrppsrgg rgaararetr rqprhrsgrr maeaisctln cscqsfkpgk inhrqcdqck

61 hgwvahalsk Irippmypts qveivqsnvv fdisslmlyg tqaipvrlki lldrlfsvlk

121 qdevlqilha Idwtlqdyir gyvlqdasgk vldhwsimts eeevatlqqf Irfgetksiv

181 elmaiqekee qsiiippsta nvdirafies cshrssslpt pvdkgnpssi hpfenlisnm

241 tfmlpfqffn plppaligsl peqymleqgh dqsqdpkqev hgpfpdssfl tssstpfqve

301 kdqclncpda itkkedsthl sdsssynivt kfertqlspe akvkpernsl gtkkgrvfct

361 acektfydkg tlkihynavh Ikikhkctie gcnmvfsslr srnrhsanpn prlhmpmnrn 421 nrdkdlrnsl nlassenykc pgftvtspdc rpppsypgsg edskgqpafp nigqngvlfp

481 nlktvqpvlp fyrspatpae vantpgilps Ipllsssipe qlisnempfd alpkkksrks

541 smpikiekea veianekrhn Issdedmplq vvsedeqeac spqshrvsee qhvqsgglgk

601 pfpegerpch resviessga isqtpeqath nsereteqtp alimvpreve dgghehyftp

661 gmepqvpfsd ymelqqrlla gglfsalsnr gmafpcleds kelehvgqha larqieenrf

721 qcdickktfk nacsvkihhk nmhvkemhtc tvegcnatfp srrsrdrhss nlnlhqkals

781 qealessedh fraayllkdv akeayqdvaf tqqasqtsvi fkgtsrmgsl vypitqvhsa

841 slesynsgpl segtildlst tssmksesss hsswdsdgvs eegtvlmeds dgncegsslv

901 pgedeypicv Imekadqsla slpsglpitc hlcqktysnk gtfrahyktv hlrqlhkckv

961 pgcntmfssv rsrnrhsqnp nlhkslassp shlq

Basonuclin 1, isoform b, NP_001288135.1 (SEQ ID NO: 43)

1 mrcrnmffsf kaslcgcgaa tapsltaisc tlncscqsfk pgkinhrqcd qckhgwvaha

61 Isklrippmy ptsqveivqs nvvfdisslm lygtqaipvr Ikilldrlfs vlkqdevlqi

121 lhaldwtiqd yirgyvlqda sgkvldhwsi mtseeevatl qqflrfgetk sivelmaiqe

181 keeqsiiipp stanvdiraf iescshrsss Iptpvdkgnp ssihpfenli snmtfmlpfq

241 ffnplppali gslpeqymle qghdqsqdpk qevhgpfpds sfltssstpf qvekdqclnc

301 pdaitkkeds thlsdsssyn ivtkfertql speakvkper nslgtkkgrv fctacektfy

361 dkgtlkihyn avhlkikhkc tiegcnmvfs slrsrnrhsa npnprlhmpm nrnnrdkdlr

421 nslnlassen ykcpgftvts pdcrpppsyp gsgedskgqp afpnigqngv Ifpnlktvqp

481 vlpfyrspat paevantpgi Ipslpllsss ipeqlisnem pfdalpkkks rkssmpikie

541 keaveianek rhnlssdedm plqvvsedeq eacspqshrv seeqhvqsgg Igkpfpeger

601 pchresvies sgaisqtpeq athnserete qtpalimvpr evedgghehy ftpgmepqvp

661 fsdymelqqr llagglfsal snrgmafpcl edskelehvg qhalarqiee nrfqcdickk

721 tfknacsvki hhknmhvkem htctvegcna tfpsrrsrdr hssnlnlhqk alsqealess

781 edhfraayll kdvakeayqd vaftqqasqt svifkgtsrm gslvypitqv hsaslesyns

841 gplsegtild Isttssmkse ssshsswdsd gvseegtvlm edsdgncegs slvpgedeyp

901 icvlmekadq slaslpsglp itchlcqkty snkgtfrahy ktvhlrqlhk ckvpgcntmf

961 ssvrsrnrhs qnpnlhksla sspshlq

BPI fold containing family A member 1, precursor, NP_001230122.1, NP_057667.1, NP_570913.1 (SEQ ID NO: 44)

1 mfqtgglivf ygllaqtmaq fgglpvpldq tlplnvnpal plsptglags Itnalsngll

61 sggllgilen Iplldilkpg ggtsggllgg llgkvtsvip glnniidikv tdpqllelgl

121 vqspdghrly vtiplgiklq vntplvgasl Irlavkldit aeilavrdkq erihlvlgdc

181 thspgslqis lldglgplpi qglldsltgi Inkvlpelvq gnvcplvnev Irglditlvh

241 divnmlihgl qfvikv

Calcium voltage-gated channel auxiliary subunit beta 3, isoform 1, NP_000716.2 (SEQ ID NO: 45)

1 myddsyvpgf edseagsads ytsrpsldsd vsleedresa rrevesqaqq qlerakhkpv

61 afavrtnvsy cgvldeecpv qgsgvnfeak dflhikekys ndwwigrlvk eggdiafips

121 pqrlesirlk qeqkarrsgn psslsdignr rspppslakq kqkqaehvpp ydvvpsmrpv

181 vlvgpslkgy evtdmmqkal fdflkhrfdg risitrvtad Islakrsvln npgkrtiier

241 ssarssiaev qseierifel akslqlvvld adtinhpaql aktslapiiv fvkvsspkvl

301 qrlirsrgks qmkhltvqmm aydklvqcpp esfdvilden qledacehla eylevywrat

361 hhpapgpgll gppsaipglq nqqllgerge ehsplerdsl mpsdeasess rqawtgssqr

421 ssrhleedya dayqdlyqph rqhtsglpsa nghdpqdrll aqdsehnhsd rnwqrnrpwp

481 kdsy

Calcium voltage-gated channel auxiliary subunit beta 3, isoform 2, NP_001193844.1 (SEQ ID NO: 46)

1 myddsyvpgf edseagsads ytsrpsldsd vsleedresa rrevesqaqq qlerakkysn

61 dwwigrlvke ggdiafipsp qrlesirlkq eqkarrsgnp sslsdignrr spppslakqk

121 qkqaehvppy dvvpsmrpvv Ivgpslkgye vtdmmqkalf dflkhrfdgr isitrvtadl

181 slakrsvlnn pgkrtiiers sarssiaevq seierifela kslqlvvlda dtinhpaqla

241 ktslapiivf vkvsspkvlq rlirsrgksq mkhltvqmma ydklvqcppe sfdvildenq

301 ledacehlae ylevywrath hpapgpgllg ppsaipglqn qqllgergee hsplerdslm

361 psdeasessr qawtgssqrs srhleedyad ayqdlyqphr qhtsglpsan ghdpqdrlla

421 qdsehnhsdr nwqrnrpwpk dsy

Calcium voltage-gated channel auxiliary subunit beta 3, isoform 3, NP_001193845.1 (SEQ ID NO: 47)

1 msfsdssatf llnegsadsy tsrpsldsdv sleedresar revesqaqqq lerakhkpva

61 favrtnvsyc gvldeecpvq gsgvnfeakd flhikekysn dwwigrlvke ggdiafipsp

121 qrlesirlkq eqkarrsgnp sslsdignrr spppslakqk qkqaehvppy dvvpsmrpvv 181 Ivgpslkgye vtdmmqkalf dflkhrfdgr isitrvtadl slakrsvlnn pgkrtiiers 241 sarssiaevq seierifela kslqlvvlda dtinhpaqla ktslapiivf vkvsspkvlq 301 rlirsrgksq mkhltvqmma ydklvqcppe sfdvildenq ledacehlae ylevywrath 361 hpapgpgllg ppsaipglqn qqllgergee hsplerdslm psdeasessr qawtgssqrs 421 srhleedyad ayqdlyqphr qhtsglpsan ghdpqdrlla qdsehnhsdr nwqrnrpwpk 481 dsy

Calcium voltage-gated channel auxiliary subunit beta 3, isoform 4, NP_001193846.1 (SEQ ID NO: 48)

1 megsadsyts rpsldsdvsl eedresarre vesqaqqqle rakhkpvafa vrtnvsycgv

61 Ideecpvqgs gvnfeakdfl hikekysndw wigrlvkegg diafipspqr lesirlkqeq

121 karrsgnpss Isdignrrsp ppslakqkqk qaehvppydv vpsmrpvvlv gpslkgyevt

181 dmmqkalfdf Ikhrfdgris itrvtadlsl akrsvlnnpg krtiierssa rssiaevqse

241 ierifelaks Iqlvvldadt inhpaqlakt slapiivfvk vsspkvlqrl irsrgksqmk

301 hltvqmmayd klvqcppesf dvildenqle dacehlaeyl evywrathhp apgpgllgpp

361 saipglqnqq llgergeehs plerdslmps deasessrqa wtgssqrssr hleedyaday

421 qdlyqphrqh tsglpsangh dpqdrllaqd sehnhsdrnw qrnrpwpkds y

Caspase 3, preproprotein, NP_001341706.1 , NP_001341707.1, NP_004346.3, NP_116786.1 (SEQ ID NO: 49)

1 mentensvds ksiknlepki ihgsesmdsg isldnsykmd ypemglciii nnknfhkstg

61 mtsrsgtdvd aanlretfrn Ikyevrnknd Itreeivelm rdvskedhsk rssfvcvlls

121 hgeegiifgt ngpvdlkkit nffrgdrcrs Itgkpklfii qacrgteldc gietdsgvdd

181 dmachkipve adflyaysta pgyyswrnsk dgswfiqslc amlkqyadkl efmhiltrvn

241 rkvatefesf sfdatfhakk qipcivsmlt kelyfyh

Caspase 3, isoform b, NP_001341708.1 , NP001341709.1 (SEQ ID NO: 50)

1 mdsgisldns ykmdypemgl ciiinnknfh kstgmtsrsg tdvdaanlre tfrnlkyevr

61 nkndltreei velmrdvske dhskrssfvc vllshgeegi ifgtngpvdl kkitnffrgd

121 rcrsltgkpk Ifiiqacrgt eldcgietds gvdddmachk ipveadflya ystapgyysw

181 rnskdgswfi qslcamlkqy adklefmhil trvnrkvate fesfsfdatf hakkqipciv

241 smltkelyfy h

Caspase 3, isoform c, NP_001341710.1 , NP001341711.1 (SEQ ID NO: 51)

1 mentensvds ksiknlepki ihgsesmdsg isldnsykmd ypemglciii nnknfhkstg 61 mtsrsgtdvd aanlretfrn Ikyevrnknd Itreeivelm rdvskedhsk rssfvcvlls 121 hgeegiifgt ngpvdlkkit nffrgdrcrs Itgkpklfii qviilgeiqr mapgsssrfv 181 pc

Caspase 3, isoform d, NP_001341712.1 (SEQ ID NO: 52)

1 msdalikvsm entensvdsk siknlepkii hgsesmdsgi sldnsykmdy pemglciiin

61 nknfhkstgm tsrsgtdvda anlretfrnl kyevrnkndl treeivelmr dvskedhskr

121 ssfvcvllsh geegiifgtn gpvdlkkitn ffrgdrcrsl tgkpklfiiq viilgeiqrm

181 apgsssrfvp c

Caspase 3, isoform e, NP_001341713.1 (SEQ ID NO: 53)

1 mdsgisldns ykmdypemgl ciiinnknfh kstgmtsrsg tdvdaanlre tfrnlkyevr 61 nkndltreei velmrdvske dhskrssfvc vllshgeegi ifgtngpvdl kkitnffrgd 121 rcrsltgkpk Ifiiqviilg eiqrmapgss srfvpc

Caveolin 1, isoform alpha, NP_001744.2 (SEQ ID NO: 54)

1 msggkyvdse ghlytvpire qgniykpnnk amadelsekq vydahtkeid Ivnrdpkhln

61 ddvvkidfed viaepegths fdgiwkasft tftvtkywfy rllsalfgip maliwgiyfa

121 ilsflhiwav vpciksflie iqcisrvysi yvhtvcdplf eavgkifsnv rinlqkei

Caveolin 1, isoform beta, NP_001166366.1 , NP_001166367.1, NP_001166368.1 (SEQ ID NO: 55)

1 madelsekqv ydahtkeidl vnrdpkhlnd dvvkidfedv iaepegthsf dgiwkasftt

61 ftvtkywfyr llsalfgipm aliwgiyfai Isflhiwavv pciksfliei qcisrvysiy

121 vhtvcdplfe avgkifsnvr inlqkei

Cadherin 1, isoform 1 preproprotein, NP_004351.1 (SEQ ID NO: 56)

1 mgpwsrslsa lllllqvssw Icqepepchp gfdaesytft vprrhlergr vlgrvnfedc

61 tgrqrtayfs Idtrfkvgtd gvitvkrplr fhnpqihflv yawdstyrkf stkvtlntvg

121 hhhrppphqa svsgiqaell tfpnsspglr rqkrdwvipp iscpenekgp fpknlvqiks

181 nkdkegkvfy sitgqgadtp pvgvfiiere tgwlkvtepl dreriatytl fshavssngn

241 avedpmeili tvtdqndnkp eftqevfkgs vmegalpgts vmevtatdad ddvntynaai

301 aytilsqdpe Ipdknmftin rntgvisvvt tgldresfpt ytlvvqaadl qgeglsttat

361 avitvtdtnd nppifnptty kgqvpenean vvittlkvtd adapntpawe avytilnddg

421 gqfvvttnpv nndgilktak gldfeakqqy ilhvavtnvv pfevslttst atvtvdvldv 481 neapifvppe krvevsedfg vgqeitsyta qepdtfmeqk ityriwrdta nwleinpdtg

541 aistraeldr edfehvknst ytaliiatdn gspvatgtgt lllilsdvnd napipeprti

601 ffcernpkpq viniidadlp pntspftael thgasanwti qyndptqesi ilkpkmalev

661 gdykinlklm dnqnkdqvtt levsvcdceg aagvcrkaqp veaglqipai Igilggilal

721 lililllllf Irrravvkep llppeddtrd nvyyydeegg geedqdfdls qlhrgldarp

781 evtrndvapt Imsvprylpr panpdeignf idenlkaadt dptappydsl Ivfdyegsgs

841 eaaslsslns sesdkdqdyd ylnewgnrfk kladmyggge dd

Cadherin 1, isoform 2 precursor, NP_001304113.1 (SEQ ID NO: 57)

1 mgpwsrslsa lllllqvssw Icqepepchp gfdaesytft vprrhlergr vlgrvnfedc

61 tgrqrtayfs Idtrfkvgtd gvitvkrplr fhnpqihflv yawdstyrkf stkvtlntvg

121 hhhrppphqa svsgiqaell tfpnsspglr rqkrdwvipp iscpenekgp fpknlvqiks

181 nkdkegkvfy sitgqgadtp pvgvfiiere tgwlkvtepl dreriatytl fshavssngn

241 avedpmeili tvtdqndnkp eftqevfkgs vmegalpgts vmevtatdad ddvntynaai

301 aytilsqdpe Ipdknmftin rntgvisvvt tgldresfpt ytlvvqaadl qgeglsttat

361 avitvtdtnd nppifnpttg Idfeakqqyi Ihvavtnvvp fevslttsta tvtvdvldvn

421 eapifvppek rvevsedfgv gqeitsytaq epdtfmeqki tyriwrdtan wleinpdtga

481 istraeldre dfehvknsty taliiatdng spvatgtgtl llilsdvndn apipeprtif

541 fcernpkpqv iniidadlpp ntspftaelt hgasanwtiq yndptqesii Ikpkmalevg

601 dykinlklmd nqnkdqvttl evsvcdcega agvcrkaqpv eaglqipail gilggilall

661 ililllllfl rrravvkepl Ippeddtrdn vyyydeeggg eedqdfdlsq Ihrgldarpe

721 vtrndvaptl msvprylprp anpdeignfi denlkaadtd ptappydsll vfdyegsgse

781 aaslsslnss esdkdqdydy Inewgnrfkk ladmyggged d

Cadherin 1, isoform 3, NP_001304114.1 (SEQ ID NO: 58)

1 meqkityriw rdtanwlein pdtgaistra eldredfehv knstytalii atdngspvat

61 gtgtlllils dvndnapipe prtiffcern pkpqviniid adlppntspf taelthgasa

121 nwtiqyndpt qesiilkpkm alevgdykin Iklmdnqnkd qvttlevsvc dcegaagvcr

181 kaqpveaglq ipailgilgg ilallilill lllflrrrav vkepllpped dtrdnvyyyd

241 eegggeedqd fdlsqlhrgl darpevtrnd vaptlmsvpr ylprpanpde ignfidenlk

301 aadtdptapp ydsllvfdye gsgseaasls slnssesdkd qdydylnewg nrfkkladmy

361 gggedd

Cadherin 1, isoform 4, NP_001304115.1 (SEQ ID NO: 59)

1 malevgdyki nlklmdnqnk dqvttlevsv cdcegaagvc rkaqpveagl qipailgilg

61 gilallilil llllflrrra vvkepllppe ddtrdnvyyy deegggeedq dfdlsqlhrg

121 Idarpevtrn dvaptlmsvp rylprpanpd eignfidenl kaadtdptap pydsllvfdy

181 egsgseaasl sslnssesdk dqdydylnew gnrfkkladm ygggedd

Cytochrome c oxidase subunit 8C, NP_892016.1 (SEQ ID NO: 60)

1 mpllrgrcpa rrhyrrlall glqpaprfah sgpprqrpls aaemavglvv ffttfltpaa 61 yvlgnlkqfr rn

Carnitine palmitoyltransferase 1A, isoform 1, NP_001867.2 (SEQ ID NO: 61)

1 maeahqavaf qftvtpdgid Irlshealrq iylsglhswk kkfirfkngi itgvypasps

61 swlivvvgvm ttmyakidps Igiiakinrt letancmssq tknvvsgvlf gtglwvaliv

121 tmryslkvll syhgwmfteh gkmsratkiw mgmvkifsgr kpmlysfqts Iprlpvpavk

181 dtvnrylqsv rplmkeedfk rmtalaqdfa vglgprlqwy Iklkswwatn yvsdwweeyi

241 ylrgrgplmv nsnyyamdll yilpthiqaa ragnaihail lyrrkldree ikpirllgst

301 iplcsaqwer mfntsripge etdtiqhmrd skhivvyhrg ryfkvwlyhd grllkpreme

361 qqmqrildnt sepqpgearl aaltagdrvp warcrqayfg rgknkqslda vekaaffvtl

421 deteegyrse dpdtsmdsya ksllhgrcyd rwfdksftfv vfkngkmgln aehswadapi

481 vahlweyvms idslqlgyae dghckgdinp nipyptrlqw dipgecqevi etslntanll

541 andvdfhsfp fvafgkgiik kcrtspdafv qlalqlahyk dmgkfcltye asmtrlfreg

601 rtetvrsctt escdfvramv dpaqtveqrl klfklasekh qhmyrlamtg sgidrhlfcl

661 yvvskylave spflkevlse pwrlstsqtp qqqvelfdle nnpeyvssgg gfgpvaddgy

721 gvsyilvgen linfhisskf scpetdshrf grhlkeamtd iitlfglssn skk

Carnitine palmitoyltransferase 1A, isoform 2, NP_001027017.1 (SEQ ID NO: 62)

1 maeahqavaf qftvtpdgid Irlshealrq iylsglhswk kkfirfkngi itgvypasps

61 swlivvvgvm ttmyakidps Igiiakinrt letancmssq tknvvsgvlf gtglwvaliv

121 tmryslkvll syhgwmfteh gkmsratkiw mgmvkifsgr kpmlysfqts Iprlpvpavk

181 dtvnrylqsv rplmkeedfk rmtalaqdfa vglgprlqwy Iklkswwatn yvsdwweeyi

241 ylrgrgplmv nsnyyamdll yilpthiqaa ragnaihail lyrrkldree ikpirllgst

301 iplcsaqwer mfntsripge etdtiqhmrd skhivvyhrg ryfkvwlyhd grllkpreme

361 qqmqrildnt sepqpgearl aaltagdrvp warcrqayfg rgknkqslda vekaaffvtl 421 deteegyrse dpdtsmdsya ksllhgrcyd rwfdksftfv vfkngkmgln aehswadapi

481 vahlweyvms idslqlgyae dghckgdinp nipyptrlqw dipgecqevi etslntanll

541 andvdfhsfp fvafgkgiik kcrtspdafv qlalqlahyk dmgkfcltye asmtrlfreg

601 rtetvrsctt escdfvramv dpaqtveqrl klfklasekh qhmyrlamtg sgidrhlfcl

661 yvvskylave spflkevlse pwrlstsqtp qqqvelfdle nnpeyvssgg gfgpvaddgy

721 gvsyilvgen linfhisskf scpetgiisq gpssdt

Cancer/testis antigen 1A, NP_640343.1 (SEQ ID NO: 63)

1 mqaegrgtgg stgdadgpgg pgipdgpggn aggpgeagat ggrgprgaga arasgpggga 61 prgphggaas glngccrcga rgpesrllef ylampfatpm eaelarrsla qdapplpvpg 121 vllkeftvsg niltirltaa dhrqlqlsis sclqqlsllm witqcflpvf laqppsgqrr C-X-C motif chemokine ligand 13, NP_006410.1 (SEQ ID NO: 64)

1 mkfistslll mllvsslspv qgvlevyyts Ircrcvqess vfiprrfidr iqilprgngc 61 prkeiivwkk nksivcvdpq aewiqrmmev Irkrssstlp vpvfkrkip Diacylglycerol kinase eta, isoform 1, NP_001191433.1 , NP_690874.2 (SEQ ID NO: 65)

1 magaggqhhp pgaaggaaag agaavtsaaa sagpgedssd seaeqegpqk lirkvstsgq

61 irtktsikeg qllkqtssfq rwkkryfklr grtlyyakds kslifdevdl sdasvaeast

121 knannsftii tpfrrlmlca enrkemedwi sslksvqtre pyevaqfnve hfsgmhnwya

181 csharptfcn vcreslsgvt shglscevck fkahkrcavr atnnckwttl asigkdiied

241 edgvamphqw legnlpvsak cavcdktcgs vlrlqdwkcl wcktmvhtac kdlyhpicpl

301 gqckvsiipp ialnstdsdg fcratfsfcv spllvfvnsk sgdnqgvkfl rrfkqllnpa

361 qvfdlmnggp hlglrlfqkf dnfrilvcgg dgsvgwvlse idklnlnkqc qlgvlplgtg

421 ndlarvlgwg gsydddtqlp qilekleras tkmldrwsim tyelklppka sllpgppeas

481 eefymtiyed svathltkil nsdehavvis saktlcetvk dfvakvekty dktlenavva

541 davaskcsvl nekleqllqa Ihtdsqaapv Ipglsplive edavesssee slgeskeqlg

601 ddvtkpssqk avkpreimlr anslkkavrq vieeagkvmd dptvhpcepa nqssdydste

661 tdeskeeakd dgakesitvk taprspdara syghsqtdsv pgpavaaske nlpvlntrii

721 cpglraglaa siagssiink mllanidpfg atpfidpdld svdgysekcv mnnyfgigld

781 akislefnnk reehpekcrs rtknlmwygv Igtrellqrs yknleqrvql ecdgqyiplp

841 slqgiavlni psyaggtnfw ggtkeddifa apsfddkile vvaifdsmqm avsrviklqh

901 hriaqcrtvk itifgdegvp vqvdgeawvq ppgiikivhk nraqmltrdr afestlkswe

961 dkqkcdsgkp vlrthlyihh aidlateevs qmqlcsqaae elitricdaa tihclleqel

1021 ahavnacsha Inkanprcpe sltrdtatei ainvkalyne tesllvgrvp Iqlespheer

1081 vsnalhsvev elqklteipw lyyilhpned eeppmdctkr nnrstvfriv pkfkkekvqk

1141 qktssqpgsg dtesgscean spgn

Diacylglycerol kinase eta, isoform 2, NP_821077.1 (SEQ ID NO: 66)

1 magaggqhhp pgaaggaaag agaavtsaaa sagpgedssd seaeqegpqk lirkvstsgq

61 irtktsikeg qllkqtssfq rwkkryfklr grtlyyakds kslifdevdl sdasvaeast

121 knannsftii tpfrrlmlca enrkemedwi sslksvqtre pyevaqfnve hfsgmhnwya

181 csharptfcn vcreslsgvt shglscevck fkahkrcavr atnnckwttl asigkdiied

241 edgvamphqw legnlpvsak cavcdktcgs vlrlqdwkcl wcktmvhtac kdlyhpicpl

301 gqckvsiipp ialnstdsdg fcratfsfcv spllvfvnsk sgdnqgvkfl rrfkqllnpa

361 qvfdlmnggp hlglrlfqkf dnfrilvcgg dgsvgwvlse idklnlnkqc qlgvlplgtg

421 ndlarvlgwg gsydddtqlp qilekleras tkmldrwsim tyelklppka sllpgppeas

481 eefymtiyed svathltkil nsdehavvis saktlcetvk dfvakvekty dktlenavva

541 davaskcsvl nekleqllqa Ihtdsqaapv Ipglsplive edavesssee slgeskeqlg

601 ddvtkpssqk avkpreimlr anslkkavrq vieeagkvmd dptvhpcepa nqssdydste

661 tdeskeeakd dgakesitvk taprspdara syghsqtdsv pgpavaaske nlpvlntrii

721 cpglraglaa siagssiink mllanidpfg atpfidpdld svdgysekcv mnnyfgigld

781 akislefnnk reehpekcrs rtknlmwygv Igtrellqrs yknleqrvql ecdgqyiplp

841 slqgiavlni psyaggtnfw ggtkeddifa apsfddkile vvaifdsmqm avsrviklqh

901 hriaqcrtvk itifgdegvp vqvdgeawvq ppgiikivhk nraqmltrdr afestlkswe

961 dkqkcdsgkp vlrthlyihh aidlateevs qmqlcsqaae elitricdaa tihclleqel

1021 ahavnacsha Inkanprcpe sltrdtatei ainvkalyne tesllvgrvp Iqlespheer

1081 vsnalhsvev elqklteipw lyyilhpned eeppmdctkr nnrstvfriv pkfkkekvqk

1141 qktssqpvqk wgteevaawl dllnlgeykd ifirhdirga ellhlerrdl kdlgipkvgh

1201 vkrilqgike Igrstpqsev

Diacylglycerol kinase eta, isoform 3, NP_001191434.1 (SEQ ID NO: 67)

1 mlcaenrkem edwisslksv qtrepyevaq fnvehfsgmh nwyacsharp tfcnvcresl 61 sgvtshglsc evckfkahkr cavratnnck wttlasigkd iiededgvam phqwlegnlp 121 vsakcavcdk tcgsvlrlqd wkclwcktmv htackdlyhp icplgqckvs iippialnst 181 dsdgfcratf sfcvspllvf vnsksgdnqg vkflrrfkql Inpaqvfdlm nggphlglrl

241 fqkfdnfril vcggdgsvgw vlseidklnl nkqcqlgvlp Igtgndlarv Igwggsyddd

301 tqlpqilekl erastkmldr wsimtyelkl ppkasllpgp peaseefymt iyedsvathl

361 tkilnsdeha vvissaktlc etvkdfvakv ektydktlen avvadavask csvlnekleq

421 llqalhtdsq aapvlpglsp liveedaves sseeslgesk eqlgddvtkp ssqkavkpre

481 imlranslkk avrqvieeag kvmddptvhp cepanqssdy dstetdeske eakddgakes

541 itvktaprsp darasyghsq tdsvpgpava askenlpvln triicpglra glaasiagss

601 iinkmllani dpfgatpfid pdldsvdgys ekcvmnnyfg igldakisle fnnkreehpe

661 kcrsrtknlm wygvlgtrel Iqrsyknleq rvqlecdgqy iplpslqgia vlnipsyagg

721 tnfwggtked difaapsfdd kilevvaifd smqmavsrvi klqhhriaqc rtvkitifgd

781 egvpvqvdge awvqppgiik ivhknraqml trdrafestl kswedkqkcd sgkpvlrthl

841 yihhaidlat eevsqmqlcs qaaeelitri cdaatihcll eqelahavna cshalnkanp

901 rcpesltrdt ateiainvka lynetesllv grvplqlesp heervsnalh svevelqklt

961 eipwlyyilh pnedeeppmd ctkrnnrstv frivpkfkke kvqkqktssq pvqkwgteev

1021 aawldllnlg eykdifirhd irgaellhle rrdlkntvge krdtkengkh mdlgipkvgh

1081 vkrilqgike Igrstpqsev

Diacylglycerol kinase eta, isoform 4, NP_001191435.1 (SEQ ID NO: 68)

1 mlcaenrkem edwisslksv qtrepyevaq fnvehfsgmh nwyacsharp tfcnvcresl

61 sgvtshglsc evckfkahkr cavratnnck wttlasigkd iiededgvam phqwlegnlp

121 vsakcavcdk tcgsvlrlqd wkclwcktmv htackdlyhp icplgqckvs iippialnst

181 dsdgfcratf sfcvspllvf vnsksgdnqg vkflrrfkql Inpaqvfdlm nggphlglrl

241 fqkfdnfril vcggdgsvgw vlseidklnl nkqcqlgvlp Igtgndlarv Igwggsyddd

301 tqlpqilekl erastkmldr wsimtyelkl ppkasllpgp peaseefymt iyedsvathl

361 tkilnsdeha vvissaktlc etvkdfvakv ektydktlen avvadavask csvlnekleq

421 llqalhtdsq aapvlpglsp liveedaves sseeslgesk eqlgddvtkp ssqkavkpre

481 imlranslkk avrqvieeag kvmddptvhp cepanqssdy dstetdeske eakddgakes

541 itvktaprsp darasyghsq tdsvpgpava askenlpvln triicpglra glaasiagss

601 iinkmllani dpfgatpfid pdldsvdgys ekcvmnnyfg igldakisle fnnkreehpe

661 kcrsrtknlm wygvlgtrel Iqrsyknleq rvqlecdgqy iplpslqgia vlnipsyagg

721 tnfwggtked difaapsfdd kilevvaifd smqmavsrvi klqhhriaqc rtvkitifgd

781 egvpvqvdge awvqppgiik ivhknraqml trdrafestl kswedkqkcd sgkpvlrthl

841 yihhaidlat eevsqmqlcs qaaeelitri cdaatihcll eqelahavna cshalnkanp

901 rcpesltrdt ateiainvka lynetesllv grvplqlesp heervsnalh svevelqklt

961 eipwlyyilh pnedeeppmd ctkrnnrstv frivpkfkke kvqkqktssq pvqkwgteev

1021 aawldllnlg eykdifirhd irgaellhle rrdlkdlgip kvghvkrilq gikelgrstp

1081 qsev

Diacylglycerol kinase eta, isoform 5, NP_001284358.1 (SEQ ID NO: 69)

1 mwnisqgctt gtpaptpdpp svtcaervfl esppmacpak vhtackdlyh picplgqckv

61 siippialns tdsdgfcrat fsfcvspllv fvnsksgdnq gvkflrrfkq llnpaqvfdl

121 mnggphlglr Ifqkfdnfri Ivcggdgsvg wvlseidkln Inkqcqlgvl plgtgndlar

181 vlgwggsydd dtqlpqilek lerastkmld rwsimtyelk Ippkasllpg ppeaseefym

241 tiyedsvath Itkilnsdeh avvissaktl cetvkdfvak vektydktle navvadavas

301 kcsvlnekle qllqalhtds qaapvlpgls pliveedave ssseeslges keqlgddvtk

361 pssqkavkpr eimlranslk kavrqvieea gkvmddptvh pcepanqssd ydstetdesk

421 eeakddgake sitvktaprs pdarasyghs qtdsvpgpav aaskenlpvl ntriicpglr

481 aglaasiags siinkmllan idpfgatpfi dpdldsvdgy sekcvmnnyf gigldakisl

541 efnnkreehp ekcrsrtknl mwygvlgtre llqrsyknle qrvqlecdgq yiplpslqgi

601 avlnipsyag gtnfwggtke ddifaapsfd dkilevvaif dsmqmavsrv iklqhhriaq

661 crtvkitifg degvpvqvdg eawvqppgii kivhknraqm Itrdrafest Ikswedkqkc

721 dsgkpvlrth lyihhaidla teevsqmqlc sqaaeelitr icdaatihcl leqelahavn

781 acshalnkan prcpesltrd tateiainvk alynetesll vgrvplqles pheervsnal

841 hsvevelqkl teipwlyyil hpnedeeppm dctkrnnrst vfrivpkfkk ekvqkqktss

901 qpgsgdtesg sceanspgn

Eukaryotic translation elongation factor 2, NP_001952.1 (SEQ ID NO: 70)

1 mvnftvdqir aimdkkanir nmsviahvdh gkstltdslv ckagiiasar agetrftdtr

61 kdeqerciti kstaislfye Isendlnfik qskdgagfli nlidspghvd fssevtaalr

121 vtdgalvvvd cvsgvcvqte tvlrqaiaer ikpvlmmnkm drallelqle peelyqtfqr

181 ivenvnviis tygegesgpm gnimidpvlg tvgfgsglhg waftlkqfae myvakfaakg

241 egqlgpaera kkvedmmkkl wgdryfdpan gkfsksatsp egkklprtfc qlildpifkv

301 fdaimnfkke etakliekld ikldsedkdk egkpllkavm rrwlpagdal Iqmitihlps

361 pvtaqkyrce llyegppdde aamgikscdp kgplmmyisk mvptsdkgrf yafgrvfsgl 421 vstglkvrrm gpnytpgkke dlylkprqrt rlmmgryvep ledvpcgniv glvgvdqflv

481 ktgtittfeh ahnmrvmkfs vspvvrvave aknpadlpkl veglkrlaks dpmvqciiee

541 sgehiiagag elhleiclkd leedhacipi kksdpvvsyr etvseesnvl clskspnkhn

601 rlymkarpfp dglaedidkg evsarqelkq rarylaekye wdvaearkiw cfgpdgtgpn

661 iltditkgvq ylneikdsvv agfqwatkeg alceenmrgv rfdvhdvtlh adaihrgggq

721 iiptarrcly asvltaqprl mepiylveiq cpeqvvggiy gvlnrkrghv feesqvagtp

781 mfvvkaylpv nesfgftadl rsntggqafp qcvfdhwqil pgdpfdnssr psqvvaetrk

841 rkglkegipa Idnfldkl

Eukaryotic translation initiation factor 5A, isoform A, NP_001137232.1 (SEQ ID NO: 71)

1 mcgtggtdsk trrpphrasf Ikrleskplk maddldfetg dagasatfpm qcsalrkngf

61 vvlkgrpcki vemstsktgk hghakvhlvg idiftgkkye dicpsthnmd vpnikrndfq

121 ligiqdgyls llqdsgevre dlrlpegdlg keieqkydcg eeilitvlsa mteeaavaik

181 amak

Eukaryotic translation initiation factor 5A, isoform B, NP_001137233.1, NP 001137234.1, NP 001961.1 (SEQ ID NO: 72)

1 maddldfetg dagasatfpm qcsalrkngf vvlkgrpcki vemstsktgk hghakvhlvg 61 idiftgkkye dicpsthnmd vpnikrndfq ligiqdgyls llqdsgevre dlrlpegdlg 121 keieqkydcg eeilitvlsa mteeaavaik amak Fibronect n 1, isofo m 1 pre cur: or, NP_997 647.1 (SEQ :D NO: 73) 1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq 61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi 121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck 181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy 241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqp qphp 301 qpppyghcvt dsgvvys vgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc 361 vlpf tyngrt f ys cttegrq dghlwcstts nyeqdqkys f ctdhtvlvqt rggnsngalc 421 hfpf lynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri 481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm 541 Inctcf gqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq 601 plqtypsssg pvevf itetp sqpnshpiqw napqpshis k yilrwrpkns vgrwkeatip 661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdf ttt ststpvtsnt vtgettpf sp 721 Ivatsesvte itass fvvsw vsasdtvsgf rveyelseeg depqyldlps tats vnipdl 781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr ws rpqapitg 841 yrivysps ve gsstelnlpe tans vtlsdl qpgvqyniti yaveenqest pvviqqettg 901 tprsdtvpsp rdlqf vevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt 961 f aevtglspg vtyyf kvf av shgres kplt aqqttkldap tnlqf vnetd stvlvrwtpp 1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg 1081 vf ttlqpgss ippyntevte ttivitwtpa prigf klgvr psqggeapre vtsdsgsivv 1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt 1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkes vpis 1261 dtiipevpql tdlsfvditd ssiglrwtpl nsstiigyri tvvaagegip ifedfvdssv 1321 gyytvtglep gidydis vit linggesapt tltqqtavpp ptdlr f tnig pdtmrvtwap 1381 ppsidltnfl vryspvknee dvaelsisps dnavvltnll pgteyvvsvs svyeqhestp 1441 Irgrqktgld sptgidf sdi tans f tvhwi apratitgyr irhhpehf sg rpredrvphs 1501 rnsitltnlt pgteyvvsiv alngreespl ligqqstvsd vprdlevvaa tptslliswd 1561 apavtvryyr itygetggns pvqeftvpgs kstatisglk pgvdytitvy avtgrgdspa 1621 sskpisinyr teidkpsqmq vtdvqdnsis vkwlpssspv tgyrvtttpk ngpgptktkt 1681 agpdqtemti eglqptveyv vs vyaqnpsg esqplvqtav tnidrpkgla ftdvdvdsik 1741 iawespqgqv sryrvtyssp edgihelfpa pdgeedtael qglrpgseyt vs vvalhddm 1801 esqpligtqs taipaptdlk ftqvtptsls aqwtppnvql tgyrvrvtpk ektgpmkein 1861 lapdsssvvv sglmvatkye vsvyalkdtl tsrpaqgvvt tlenvspprr arvtdatett 1921 itiswrtkte titgf qvdav pangqtpiqr tikpdvrsyt itglqpgtdy kiylytlndn 1981 arsspvvida staidapsnl rf lattpnsl Ivswqpprar itgyiikyek pgspprevvp 2041 rp rpgvteat itglepgtey tiyvialknn qksepligrk ktdelpqlvt Iphpnlhgpe 2101 ildvpstvqk tpf vthpgyd tgngiqlpgt sgqqpsvgqq mifeehgfrr ttppttatpi 2161 rhrp rp yppn vgeeiqighi predvdyhly phgpglnpna stgqealsqt tiswapfqdt 2221 seyiis chpv gtdeeplqf r vpgtstsatl tgltrgatyn iivealkdqq rhkvreevvt 2281 vgns vnegln qptddscfdp ytvshyavgd ewermsesgf kllcqclgf g sghf rcdssr 2341 wchdngvnyk igekwdrqge ngqmmsctcl gngkgef kcd pheatcyddg ktyhvgeqwq 2401 keylgaicsc tcf ggqrgwr cdncrrpgge pspegttgqs ynqysqryhq rtntnvncpi 2461 ecfmpldvqa dredsre

Fibronectin 1, isoform 3 precursor, NP_002017.1 (SEQ ID NO: 74)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt nidrpkglaf tdvdvdsiki awespqgqvs ryrvtysspe dgihelfpap

1681 dgeedtaelq glrpgseytv svvalhddme sqpligtqst aipaptdlkf tqvtptslsa

1741 qwtppnvqlt gyrvrvtpke ktgpmkeinl apdsssvvvs glmvatkyev svyalkdtlt

1801 srpaqgvvtt lenvspprra rvtdatetti tiswrtktet itgfqvdavp angqtpiqrt

1861 ikpdvrsyti tglqpgtdyk iylytlndna rsspvvidas taidapsnlr flattpnsll

1921 vswqpprari tgyiikyekp gspprevvpr prpgvteati tglepgteyt iyvialknnq

1981 ksepligrkk tdelpqlvtl phpnlhgpei Idvpstvqkt pfvthpgydt gngiqlpgts

2041 gqqpsvgqqm ifeehgfrrt tppttatpir hrprpyppnv gqealsqtti swapfqdtse

2101 yiischpvgt deeplqfrvp gtstsatltg Itrgatynii vealkdqqrh kvreevvtvg

2161 nsvneglnqp tddscfdpyt vshyavgdew ermsesgfkl Icqclgfgsg hfrcdssrwc

2221 hdngvnykig ekwdrqgeng qmmsctclgn gkgefkcdph eatcyddgkt yhvgeqwqke

2281 ylgaicsctc fggqrgwrcd ncrrpggeps pegttgqsyn qysqryhqrt ntnvncpiec

2341 fmpldvqadr edsre

Fibronectin 1, isoform 4 precursor, NP_997643.1 (SEQ ID NO: 75) 1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg 1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt nidrpkglaf tdvdvdsiki awespqgqvs ryrvtysspe dgihelfpap

1681 dgeedtaelq glrpgseytv svvalhddme sqpligtqst aipaptdlkf tqvtptslsa

1741 qwtppnvqlt gyrvrvtpke ktgpmkeinl apdsssvvvs glmvatkyev svyalkdtlt

1801 srpaqgvvtt lenvspprra rvtdatetti tiswrtktet itgfqvdavp angqtpiqrt

1861 ikpdvrsyti tglqpgtdyk iylytlndna rsspvvidas taidapsnlr flattpnsll

1921 vswqpprari tgyiikyekp gspprevvpr prpgvteati tglepgteyt iyvialknnq

1981 ksepligrkk tvqktpfvth pgydtgngiq Ipgtsgqqps vgqqmifeeh gfrrttpptt

2041 atpirhrprp yppnvgqeal sqttiswapf qdtseyiisc hpvgtdeepl qfrvpgtsts

2101 atltgltrga tyniivealk dqqrhkvree vvtvgnsvne glnqptddsc fdpytvshya

2161 vgdewermse sgfkllcqcl gfgsghfrcd ssrwchdngv nykigekwdr qgengqmmsc

2221 tclgngkgef kcdpheatcy ddgktyhvge qwqkeylgai csctcfggqr gwrcdncrrp

2281 ggepspegtt gqsynqysqr yhqrtntnvn cpiecfmpld vqadredsre

Fibronectin 1, isoform 5 precursor, NP_997641.1 (SEQ ID NO: 76)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt tipaptdlkf tqvtptslsa qwtppnvqlt gyrvrvtpke ktgpmkeinl

1681 apdsssvvvs glmvatkyev svyalkdtlt srpaqgvvtt lenvspprra rvtdatetti

1741 tiswrtktet itgfqvdavp angqtpiqrt ikpdvrsyti tglqpgtdyk iylytlndna

1801 rsspvvidas taidapsnlr flattpnsll vswqpprari tgyiikyekp gspprevvpr

1861 prpgvteati tglepgteyt iyvialknnq ksepligrkk tdelpqlvtl phpnlhgpei

1921 Idvpstvqkt pfvthpgydt gngiqlpgts gqqpsvgqqm ifeehgfrrt tppttatpir

1981 hrprpyppnv geeiqighip redvdyhlyp hgpglnpnas tgqealsqtt iswapfqdts

2041 eyiischpvg tdeeplqfrv pgtstsatlt gltrgatyni ivealkdqqr hkvreevvtv

2101 gnsvneglnq ptddscfdpy tvshyavgde wermsesgfk llcqclgfgs ghfrcdssrw

2161 chdngvnyki gekwdrqgen gqmmsctclg ngkgefkcdp heatcyddgk tyhvgeqwqk

2221 eylgaicsct cfggqrgwrc dncrrpggep spegttgqsy nqysqryhqr tntnvncpie

2281 cfmpldvqad redsre Fibronectin 1, isoform 6 precursor, NP_997639.1 (SEQ ID NO: 77)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt tipaptdlkf tqvtptslsa qwtppnvqlt gyrvrvtpke ktgpmkeinl

1681 apdsssvvvs glmvatkyev svyalkdtlt srpaqgvvtt lenvspprra rvtdatetti

1741 tiswrtktet itgfqvdavp angqtpiqrt ikpdvrsyti tglqpgtdyk iylytlndna

1801 rsspvvidas taidapsnlr flattpnsll vswqpprari tgyiikyekp gspprevvpr

1861 prpgvteati tglepgteyt iyvialknnq ksepligrkk tgqealsqtt iswapfqdts

1921 eyiischpvg tdeeplqfrv pgtstsatlt gltrgatyni ivealkdqqr hkvreevvtv

1981 gnsvneglnq ptddscfdpy tvshyavgde wermsesgfk llcqclgfgs ghfrcdssrw

2041 chdngvnyki gekwdrqgen gqmmsctclg ngkgefkcdp heatcyddgk tyhvgeqwqk

2101 eylgaicsct cfggqrgwrc dncrrpggep spegttgqsy nqysqryhqr tntnvncpie

2161 cfmpldvqad redsre

Fibronectin 1, isoform 7 precursor, NP_473375.2 (SEQ ID NO: 78)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpvsi pprnlgy

Fibronectin 1, isoform 8 precursor, NP_001293058.1 (SEQ ID NO: 79)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq 601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipevpql tdlsfvditd ssiglrwtpl nsstiigyri tvvaagegip ifedfvdssv

1321 gyytvtglep gidydisvit linggesapt tltqqtavpp ptdlrftnig pdtmrvtwap

1381 ppsidltnfl vryspvknee dvaelsisps dnavvltnll pgteyvvsvs svyeqhestp

1441 Irgrqktgld sptgidfsdi tansftvhwi apratitgyr irhhpehfsg rpredrvphs

1501 rnsitltnlt pgteyvvsiv alngreespl ligqqstvsd vprdlevvaa tptslliswd

1561 apavtvryyr itygetggns pvqeftvpgs kstatisglk pgvdytitvy avtgrgdspa

1621 sskpisinyr teidkpsqmq vtdvqdnsis vkwlpssspv tgyrvtttpk ngpgptktkt

1681 agpdqtemti eglqptveyv vsvyaqnpsg esqplvqtav tnidrpkgla ftdvdvdsik

1741 iawespqgqv sryrvtyssp edgihelfpa pdgeedtael qglrpgseyt vsvvalhddm

1801 esqpligtqs taipaptdlk ftqvtptsls aqwtppnvql tgyrvrvtpk ektgpmkein

1861 lapdsssvvv sglmvatkye vsvyalkdtl tsrpaqgvvt tlenvspprr arvtdatett

1921 itiswrtkte titgfqvdav pangqtpiqr tikpdvrsyt itglqpgtdy kiylytlndn

1981 arsspvvida staidapsnl rflattpnsl Ivswqpprar itgyiikyek pgspprevvp

2041 rprpgvteat itglepgtey tiyvialknn qksepligrk ktdelpqlvt Iphpnlhgpe

2101 ildvpstvqk tpfvthpgyd tgngiqlpgt sgqqpsvgqq mifeehgfrr ttppttatpi

2161 rhrprpyppn vgqealsqtt iswapfqdts eyiischpvg tdeeplqfrv pgtstsatlt

2221 gltrgatyni ivealkdqqr hkvreevvtv gnsvneglnq ptddscfdpy tvshyavgde

2281 wermsesgfk llcqclgfgs ghfrcdssrw chdngvnyki gekwdrqgen gqmmsctclg

2341 ngkgefkcdp heatcyddgk tyhvgeqwqk eylgaicsct cfggqrgwrc dncrrpggep

2401 spegttgqsy nqysqryhqr tntnvncpie cfmpldvqad redsre

Fibronectin 1, isoform 9 precursor, NP_001293059.1 (SEQ ID NO: 80)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipevpql tdlsfvditd ssiglrwtpl nsstiigyri tvvaagegip ifedfvdssv

1321 gyytvtglep gidydisvit linggesapt tltqqtavpp ptdlrftnig pdtmrvtwap

1381 ppsidltnfl vryspvknee dvaelsisps dnavvltnll pgteyvvsvs svyeqhestp

1441 Irgrqktgld sptgidfsdi tansftvhwi apratitgyr irhhpehfsg rpredrvphs

1501 rnsitltnlt pgteyvvsiv alngreespl ligqqstvsd vprdlevvaa tptslliswd

1561 apavtvryyr itygetggns pvqeftvpgs kstatisglk pgvdytitvy avtgrgdspa

1621 sskpisinyr teidkpsqmq vtdvqdnsis vkwlpssspv tgyrvtttpk ngpgptktkt

1681 agpdqtemti eglqptveyv vsvyaqnpsg esqplvqtav ttipaptdlk ftqvtptsls 1741 aqwtppnvql tgyrvrvtpk ektgpmkein lapdsssvvv sglmvatkye vsvyalkdtl

1801 tsrpaqgvvt tlenvspprr arvtdatett itiswrtkte titgfqvdav pangqtpiqr

1861 tikpdvrsyt itglqpgtdy kiylytlndn arsspvvida staidapsnl rflattpnsl

1921 Ivswqpprar itgyiikyek pgspprevvp rprpgvteat itglepgtey tiyvialknn

1981 qksepligrk ktgqealsqt tiswapfqdt seyiischpv gtdeeplqfr vpgtstsatl

2041 tgltrgatyn iivealkdqq rhkvreevvt vgnsvnegln qptddscfdp ytvshyavgd

2101 ewermsesgf kllcqclgfg sghfrcdssr wchdngvnyk igekwdrqge ngqmmsctcl

2161 gngkgefkcd pheatcyddg ktyhvgeqwq keylgaicsc tcfggqrgwr cdncrrpgge

2221 pspegttgqs ynqysqryhq rtntnvncpi ecfmpldvqa dredsre

Fibronectin 1, isoform 10 precursor, NP_001293060.1 (SEQ ID NO: 81)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp

721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt tipaptdlkf tqvtptslsa qwtppnvqlt gyrvrvtpke ktgpmkeinl

1681 apdsssvvvs glmvatkyev svyalkdtlt srpaqgvvtt lenvspprra rvtdatetti

1741 tiswrtktet itgfqvdavp angqtpiqrt ikpdvrsyti tglqpgtdyk iylytlndna

1801 rsspvvidas taidapsnlr flattpnsll vswqpprari tgyiikyekp gspprevvpr

1861 prpgvteati tglepgteyt iyvialknnq ksepligrkk tdelpqlvtl phpnlhgpei

1921 Idvpstvqkt pfvthpgydt gngiqlpgts gqqpsvgqqm ifeehgfrrt tppttatpir

1981 hrprpyppnv gqealsqtti swapfqdtse yiischpvgt deeplqfrvp gtstsatltg

2041 Itrgatynii vealkdqqrh kvreevvtvg nsvneglnqp tddscfdpyt vshyavgdew

2101 ermsesgfkl Icqclgfgsg hfrcdssrwc hdngvnykig ekwdrqgeng qmmsctclgn

2161 gkgefkcdph eatcyddgkt yhvgeqwqke ylgaicsctc fggqrgwrcd ncrrpggeps

2221 pegttgqsyn qysqryhqrt ntnvncpiec fmpldvqadr edsre

Fibronectin 1, isoform 11 precursor, NP_001293061.1 (SEQ ID NO: 82)

1 mlrgpgpgll llavqclgta vpstgasksk rqaqqmvqpq spvavsqskp gcydngkhyq

61 inqqwertyl gnalvctcyg gsrgfncesk peaeetcfdk ytgntyrvgd tyerpkdsmi

121 wdctcigagr grisctianr cheggqsyki gdtwrrphet ggymlecvcl gngkgewtck

181 piaekcfdha agtsyvvget wekpyqgwmm vdctclgegs gritctsrnr cndqdtrtsy

241 rigdtwskkd nrgnllqcic tgngrgewkc erhtsvqtts sgsgpftdvr aavyqpqphp

301 qpppyghcvt dsgvvysvgm qwlktqgnkq mlctclgngv scqetavtqt yggnsngepc

361 vlpftyngrt fyscttegrq dghlwcstts nyeqdqkysf ctdhtvlvqt rggnsngalc

421 hfpflynnhn ytdctsegrr dnmkwcgttq nydadqkfgf cpmaaheeic ttnegvmyri

481 gdqwdkqhdm ghmmrctcvg ngrgewtcia ysqlrdqciv dditynvndt fhkrheeghm

541 Inctcfgqgr grwkcdpvdq cqdsetgtfy qigdswekyv hgvryqcycy grgigewhcq

601 plqtypsssg pvevfitetp sqpnshpiqw napqpshisk yilrwrpkns vgrwkeatip

661 ghlnsytikg Ikpgvvyegq lisiqqyghq evtrfdfttt ststpvtsnt vtgettpfsp 721 Ivatsesvte itassfvvsw vsasdtvsgf rveyelseeg depqyldlps tatsvnipdl

781 Ipgrkyivnv yqisedgeqs lilstsqtta pdappdptvd qvddtsivvr wsrpqapitg

841 yrivyspsve gsstelnlpe tansvtlsdl qpgvqyniti yaveenqest pvviqqettg

901 tprsdtvpsp rdlqfvevtd vkvtimwtpp esavtgyrvd vipvnlpgeh gqrlpisrnt

961 faevtglspg vtyyfkvfav shgreskplt aqqttkldap tnlqfvnetd stvlvrwtpp

1021 raqitgyrlt vgltrrgqpr qynvgpsvsk yplrnlqpas eytvslvaik gnqespkatg

1081 vfttlqpgss ippyntevte ttivitwtpa prigfklgvr psqggeapre vtsdsgsivv

1141 sgltpgveyv ytiqvlrdgq erdapivnkv vtplspptnl hleanpdtgv Itvswerstt

1201 pditgyritt tptngqqgns leevvhadqs sctfdnlspg leynvsvytv kddkesvpis

1261 dtiipavppp tdlrftnigp dtmrvtwapp psidltnflv ryspvkneed vaelsispsd

1321 navvltnllp gteyvvsvss vyeqhestpl rgrqktglds ptgidfsdit ansftvhwia

1381 pratitgyri rhhpehfsgr predrvphsr nsitltnltp gteyvvsiva Ingreespll

1441 igqqstvsdv prdlevvaat ptslliswda pavtvryyri tygetggnsp vqeftvpgsk

1501 statisglkp gvdytitvya vtgrgdspas skpisinyrt eidkpsqmqv tdvqdnsisv

1561 kwlpssspvt gyrvtttpkn gpgptktkta gpdqtemtie glqptveyvv svyaqnpsge

1621 sqplvqtavt tipaptdlkf tqvtptslsa qwtppnvqlt gyrvrvtpke ktgpmkeinl

1681 apdsssvvvs glmvatkyev svyalkdtlt srpaqgvvtt lenvspprra rvtdatetti

1741 tiswrtktet itgfqvdavp angqtpiqrt ikpdvrsyti tglqpgtdyk iylytlndna

1801 rsspvvidas taidapsnlr flattpnsll vswqpprari tgyiikyekp gspprevvpr

1861 prpgvteati tglepgteyt iyvialknnq ksepligrkk tvqktpfvth pgydtgngiq

1921 Ipgtsgqqps vgqqmifeeh gfrrttpptt atpirhrprp yppnvgqeal sqttiswapf

1981 qdtseyiisc hpvgtdeepl qfrvpgtsts atltgltrga tyniivealk dqqrhkvree

2041 vvtvgnsvne glnqptddsc fdpytvshya vgdewermse sgfkllcqcl gfgsghfrcd

2101 ssrwchdngv nykigekwdr qgengqmmsc tclgngkgef kcdpheatcy ddgktyhvge

2161 qwqkeylgai csctcfggqr gwrcdncrrp ggepspegtt gqsynqysqr yhqrtntnvn

2221 cpiecfmpld vqadredsre

Major histocompatibility complex, class II, DR beta 1, precursor,

NP_001230894.1 (SEQ ID NO: 83)

1 mvclrlpggs cmavltvtlm vlssplalag dtrprfleys tsechffngt ervryldryf 61 hnqeenvrfd sdvgefravt elgrpdaeyw nsqkdlleqk rgrvdnycrh nygvvesftv

121 qrrvhpkvtv ypsktqplqh hnllvcsvsg fypgsievrw frngqeektg vvstglihng

181 dwtfqtlvml etvprsgevy tcqvehpsvt spltvewrar sesaqskmls gvggfvlgll

241 flgaglfiyf rnqkghsglq prgfls

Major histocompatibility complex, class II, DR beta 1, precursor, NP_001346122.1 (SEQ ID NO: 84)

1 mvclklpggs cmaaltvtlm vlssplalag dtqprflwqg kykchffngt ervqflerlf 61 ynqeefvrfd sdvgeyravt elgrpvaesw nsqkdiledr rgqvdtvcrh nygvgesftv

121 qrrvhpevtv ypaktqplqh hnllvcsvsg fypgsievrw frngqeekag vvstgliqng

181 dwtfqtlvml etvprsgevy tcqvehpsvm spltvewrar sesaqskmls gvggfvlgll

241 flgaglfiyf rnqkghsglq ptgfls

Major histocompatibility complex, class II, DR beta 1, precursor, NP_001346123.1 (SEQ ID NO: 85)

1 mvclkfpggs cmaaltvtlm vlssplalag dtrprfleqv khechffngt ervrfldryf 61 yhqeeyvrfd sdvgeyravt elgrpdaeyw nsqkdlleqr raevdtycrh nygvvesftv

121 qrrvypevtv ypaktqplqh hnllvcsvng fypgsievrw frngqeektg vvstgliqng

181 dwtfqtlvml etvprsgevy tcqvehpslt spltvewrar sesaqskmls gvggfvlgll

241 flgaglfiyf rnqkghsglq ptgfls

Major histocompatibility complex, class II, DR beta 1, precursor, NP_002115.2 (SEQ ID NO: 86)

1 mvclklpggs cmtaltvtlm vlssplalsg dtrprflwqp krechffngt ervrfldryf 61 ynqeesvrfd sdvgefravt elgrpdaeyw nsqkdileqa raavdtycrh nygvvesftv

121 qrrvqpkvtv ypsktqplqh hnllvcsvsg fypgsievrw flngqeekag mvstgliqng

181 dwtfqtlvml etvprsgevy tcqvehpsvt spltvewrar sesaqskmls gvggfvlgll

241 flgaglfiyf rnqkghsglq ptgfls

Major histocompatibility complex, class II, DR beta 5, precursor, NP_002116.2 (SEQ ID NO: 87)

1 mvclklpggs ymakltvtlm vlssplalag dtrprflqqd kyechffngt ervrflhrdi 61 ynqeedlrfd sdvgeyravt elgrpdaeyw nsqkdfledr raavdtycrh nygvgesftv

121 qrrvepkvtv ypartqtlqh hnllvcsvng fypgsievrw frnsqeekag vvstgliqng

181 dwtfqtlvml etvprsgevy tcqvehpsvt spltvewraq sesaqskmls gvggfvlgll

241 flgaglfiyf knqkghsglh ptglvs Hydroxysteroid 17-beta dehydrogenase 3, NP_000188.1 (SEQ ID NO: 88)

1 mgdvleqffi Itgllvclac lakcvrfsrc vllnywkvlp ksflrsmgqw avitgagdgi

61 gkaysfelak rglnvvlisr tlekleaiat eierttgrsv kiiqadftkd diyehikekl

121 agleigilvn nvgmlpnllp shflnapdei qslihcnits vvkmtqlilk hmesrqkgli

181 Inissgialf pwplysmysa skafvcafsk alqeeykake viiqvltpya vstamtkyln

241 tnvitktade fvkeslnyvt iggetcgcla heilagflsl ipawafysga fqrlllthyv

301 aylklntkvr

Insulin degrading enzyme, isoform 1, NP_004960.2 (SEQ ID NO: 89)

1 mryrlawllh palpstfrsv Igarlppper Icgfqkktys kmnnpaikri gnhitksped

61 kreyrglela ngikvllisd pttdkssaal dvhigslsdp pniaglshfc ehmlflgtkk

121 ypkeneysqf Isehagssna ftsgehtnyy fdvshehleg aldrfaqffl cplfdesckd

181 revnavdseh eknvmndawr Ifqlekatgn pkhpfskfgt gnkytletrp nqegidvrqe

241 llkfhsayys snlmavcvlg reslddltnl vvklfseven knvplpefpe hpfqeehlkq

301 lykivpikdi rnlyvtfpip dlqkyyksnp ghylghligh egpgsllsel kskgwvntlv

361 ggqkegargf mffiinvdlt eegllhvedi ilhmfqyiqk Iraegpqewv fqeckdlnav

421 afrfkdkerp rgytskiagi Ihyypleevl taeylleefr pdliemvldk Irpenvrvai

481 vsksfegktd rteewygtqy kqeaipdevi kkwqnadlng kfklptknef iptnfeilpl

541 ekeatpypal ikdtamsklw fkqddkfflp kaclnfeffs pfayvdplhc nmaylylell

601 kdslneyaya aelaglsydl qntiygmyls vkgyndkqpi llkkiiekma tfeidekrfe

661 iikeaymrsl nnfraeqphq hamyylrllm tevawtkdel kealddvtlp rlkafipqll

721 srlhieallh gnitkqaalg imqmvedtli ehahtkpllp sqlvryrevq Ipdrgwfvyq

781 qrnevhnncg ieiyyqtdmq stsenmflel fcqiisepcf ntlrtkeqlg yivfsgprra

841 ngiqglrfii qsekpphyle srveaflitm eksiedmtee afqkhiqala irrldkpkkl

901 saecakywge iisqqynfdr dntevaylkt Itkediikfy kemlavdapr rhkvsvhvla

961 remdscpvvg efpcqndinl sqapalpqpe viqnmtefkr glplfplvkp hinfmaakl

Insulin degrading enzyme, isoform 2, NP_001159418.1 (SEQ ID NO: 90)

1 msklwfkqdd kfflpkacln feffspfayv dplhcnmayl ylellkdsln eyayaaelag

61 Isydlqntiy gmylsvkgyn dkqpillkki iekmatfeid ekrfeiikea ymrslnnfra

121 eqphqhamyy Irllmtevaw tkdelkeald dvtlprlkaf ipqllsrlhi eallhgnitk

181 qaalgimqmv edtliehaht kpllpsqlvr yrevqlpdrg wfvyqqrnev hnncgieiyy

241 qtdmqstsen mflelfcqii sepcfntlrt keqlgyivfs gprrangiqg Irfiiqsekp

301 phylesrvea flitmeksie dmteeafqkh iqalairrld kpkklsaeca kywgeiisqq

361 ynfdrdntev aylktltked iikfykemla vdaprrhkvs vhvlaremds cpvvgefpcq

421 ndinlsqapa Ipqpeviqnm tefkrglplf plvkphinfm aakl

Insulin degrading enzyme, isoform 3, NP_001309722.1 (SEQ ID NO: 91)

1 mryrlawllh palpstfrsv Igarlppper Icgfqkktys kmnnpaikri gnhitksped

61 kreyrglela ngikvllisd pttdkssaal dvhigslsdp pniaglshfc ehmlflgtkk

121 ypkeneysqf Isehagssna ftsgehtnyy fdvshehleg aldrfaqffl cplfdesckd

181 revnavdseh eknvmndawr Ifqlekatgn pkhpfskfgt gnkytletrp nqegidvrqe

241 llkfhsayys snlmavcvlg reslddltnl vvklfseven knvplpefpe hpfqeehlkq

301 lykivpikdi rnlyvtfpip dlqkyyksnp ghylghligh egpgsllsel kskgwvntlv

361 ggqkegargf mffiinvdlt eegllhvedi ilhmfqyiqk Iraegpqewv fqeckdlnav

421 afrfkdkerp rgytskiagi Ihyypleevl taeylleefr pdliemvldk Irpenvrvai

481 vsksfegktd rteewygtqy kqeaipdevi kkwqnadlng kfklptknef iptnfeilpl

541 ekeatpypal ikdtamsklw fkqddkfflp kaclnfeffs ryiyadplhc nmtylfirll

601 kddlkeytya arlsglsygi asgmnaills vkgyndkqpi llkkiiekma tfeidekrfe

661 iikeaymrsl nnfraeqphq hamyylrllm tevawtkdel kealddvtlp rlkafipqll

721 srlhieallh gnitkqaalg imqmvedtli ehahtkpllp sqlvryrevq Ipdrgwfvyq

781 qrnevhnncg ieiyyqtdmq stsenmflel fcqiisepcf ntlrtkeqlg yivfsgprra

841 ngiqglrfii qsekpphyle srveaflitm eksiedmtee afqkhiqala irrldkpkkl

901 saecakywge iisqqynfdr dntevaylkt Itkediikfy kemlavdapr rhkvsvhvla

961 remdscpvvg efpcqndinl sqapalpqpe viqnmtefkr glplfplvkp hinfmaakl

Insulin degrading enzyme, isoform 4, NP_001309723.1 (SEQ ID NO: 92)

1 mryrlawllh palpstfrsv Igarlppper Icgfqkktys kmnnpaikri gnhitksped

61 kreyrglela ngikvllisd pttdkssaal dvhigslsdp pniaglshfc ehmlflgtkk

121 ypkeneysqf Isehagssna ftsgehtnyy fdvshehleg aldrfaqffl cplfdesckd

181 revnavdseh eknvmndawr Ifqlekatgn pkhpfskfgt greslddltn Ivvklfseve

241 nknvplpefp ehpfqeehlk qlykivpikd irnlyvtfpi pdlqkyyksn pghylghlig

301 hegpgsllse Ikskgwvntl vggqkegarg fmffiinvdl teegllhved iilhmfqyiq

361 klraegpqew vfqeckdlna vafrfkdker prgytskiag ilhyypleev Itaeylleef

421 rpdliemvld klrpenvrva ivsksfegkt drteewygtq ykqeaipdev ikkwqnadln 481 gkfklptkne fiptnfeilp lekeatpypa likdtamskl wfkqddkffl pkaclnfeff

541 spfayvdplh cnmaylylel Ikdslneyay aaelaglsyd Iqntiygmyl svkgyndkqp

601 illkkiiekm atfeidekrf eiikeaymrs Innfraeqph qhamyylrll mtevawtkde

661 Ikealddvtl prlkafipql Isrlhieall hgnitkqaal gimqmvedtl iehahtkpll

721 psqlvryrev qlpdrgwfvy qqrnevhnnc gieiyyqtdm qstsenmfle Ifcqiisepc

781 fntlrtkeql gyivfsgprr angiqglrfi iqsekpphyl esrveaflit meksiedmte

841 eafqkhiqal airrldkpkk Isaecakywg eiisqqynfd rdntevaylk tltkediikf

901 ykemlavdap rrhkvsvhvl aremdscpvv gefpcqndin Isqapalpqp eviqnmtefk

961 rglplfplvk phinfmaakl

Insulin degrading enzyme, isoform 5, NP_001309724.1, NP_001309725.1 (SEQ ID NO: 93)

1 mnnpaikrig nhitkspedk reyrglelan gikvllisdp ttdkssaald vhigslsdpp

61 niaglshfce hmlflgtkky pkeneysqfl sehagssnaf tsgehtnyyf dvshehlega

121 Idrfaqfflc plfdesckdr evnavdsehe knvmndawrl fqlekatgnp khpfskfgtg

181 nkytletrpn qegidvrqel Ikfhsayyss nlmavcvlgr eslddltnlv vklfsevenk

241 nvplpefpeh pfqeehlkql ykivpikdir nlyvtfpipd Iqkyyksnpg hylghlighe

301 gpgsllselk skgwvntlvg gqkegargfm ffiinvdlte egllhvedii Ihmfqyiqkl

361 raegpqewvf qeckdlnava frfkdkerpr gytskiagil hyypleevlt aeylleefrp

421 dliemvldkl rpenvrvaiv sksfegktdr teewygtqyk qeaipdevik kwqnadlngk

481 fklptknefi ptnfeilple keatpypali kdtamsklwf kqddkfflpk aclnfeffsp

541 fayvdplhcn maylylellk dslneyayaa elaglsydlq ntiygmylsv kgyndkqpil

601 Ikkiiekmat feidekrfei ikeaymrsln nfraeqphqh amyylrllmt evawtkdelk

661 ealddvtlpr Ikafipqlls rlhieallhg nitkqaalgi mqmvedtlie hahtkpllps

721 qlvryrevql pdrgwfvyqq rnevhnncgi eiyyqtdmqs tsenmflelf cqiisepcfn

781 tlrtkeqlgy ivfsgprran giqglrfiiq sekpphyles rveaflitme ksiedmteea

841 fqkhiqalai rrldkpkkls aecakywgei isqqynfdrd ntevaylktl tkediikfyk

901 emlavdaprr hkvsvhvlar emdscpvvge fpcqndinls qapalpqpev iqnmtefkrg

961 Iplfplvkph infmaakl

Insulin degrading enzyme, isoform 6, NP_001309726.1 (SEQ ID NO: 94)

1 msklwfkqdd kfflpkacln feffsryiya dplhcnmtyl firllkddlk eytyaarlsg

61 Isygiasgmn aillsvkgyn dkqpillkki iekmatfeid ekrfeiikea ymrslnnfra

121 eqphqhamyy Irllmtevaw tkdelkeald dvtlprlkaf ipqllsrlhi eallhgnitk

181 qaalgimqmv edtliehaht kpllpsqlvr yrevqlpdrg wfvyqqrnev hnncgieiyy

241 qtdmqstsen mflelfcqii sepcfntlrt keqlgyivfs gprrangiqg Irfiiqsekp

301 phylesrvea flitmeksie dmteeafqkh iqalairrld kpkklsaeca kywgeiisqq

361 ynfdrdntev aylktltked iikfykemla vdaprrhkvs vhvlaremds cpvvgefpcq

421 ndinlsqapa Ipqpeviqnm tefkrglplf plvkphinfm aakl

Indoleamine 2 , 3-dioxygenase 1, NP_002155.1 (SEQ ID NO: 95)

1 mahamenswt iskeyhidee vgfalpnpqe nlpdfyndwm fiakhlpdli esgqlrerve

61 klnmlsidhl tdhksqrlar Ivlgcitmay vwgkghgdvr kvlprniavp ycqlskklel

121 ppilvyadcv lanwkkkdpn kpltyenmdv Ifsfrdgdcs kgfflvsllv eiaaasaikv

181 iptvfkamqm qerdtllkal leiascleka Iqvfhqihdh vnpkaffsvl riylsgwkgn

241 pqlsdglvye gfwedpkefa ggsagqssvf qcfdvllgiq qtaggghaaq flqdmrrymp

301 pahrnflcsl esnpsvrefv Iskgdaglre aydacvkalv slrsyhlqiv tkyilipasq

361 qpkenktsed pskleakgtg gtdlmnflkt vrstteksll keg

Insulin like growth factor binding protein 5, precursor, NP_000590.1 (SEQ ID NO: 96)

1 mvlltavlll laayagpaqs Igsfvhcepc dekalsmcpp splgcelvke pgcgccmtca

61 laegqscgvy tercaqglrc Iprqdeekpl hallhgrgvc Ineksyreqv kierdsrehe

121 epttsemaee tyspkifrpk htriselkae avkkdrrkkl tqskfvggae ntahpriisa

181 pemrqeseqg pcrrhmeasl qelkasprmv pravylpncd rkgfykrkqc kpsrgrkrgi

241 cwcvdkygmk Ipgmeyvdgd fqchtfdssn ve

Insulin like growth factor binding protein 7, isoform 1 precursor, NP_001544.1 (SEQ ID NO: 97)

1 merpslrall Igaaglllll Iplssssssd tcgpcepasc pplpplgcll getrdacgcc

61 pmcargegep cggggagrgy capgmecvks rkrrkgkaga aaggpgvsgv cvcksrypvc

121 gsdgttypsg cqlraasqra esrgekaitq vskgtceqgp sivtppkdiw nvtgaqvyls

181 cevigiptpv liwnkvkrgh ygvqrtellp gdrdnlaiqt rggpekhevt gwvlvsplsk

241 edageyecha snsqgqasas akitvvdalh eipvkkgega el

Insulin like growth factor binding protein 7, isoform 2 precursor, NP 001240764.1 (SEQ ID NO: 98) 1 merpslrall Igaaglllll Iplssssssd tcgpcepasc pplpplgcll getrdacgcc

61 pmcargegep cggggagrgy capgmecvks rkrrkgkaga aaggpgvsgv cvcksrypvc

121 gsdgttypsg cqlraasqra esrgekaitq vskgtceqgp sivtppkdiw nvtgaqvyls

181 cevigiptpv liwnkvkrgh ygvqrtellp gdrdnlaiqt rggpekhevt gwvlvsplsk

241 edageyecha snsqgqasas akitvvdalh eipvkkgtq

Potassium two pore domain channel subfamily K member 1, NP_002236.1 (SEQ ID NO: 99)

1 mlqslagssc vrlverhrsa wcfgflvlgy llylvfgavv fssvelpyed llrqelrklk

61 rrfleehecl seqqleqflg rvleasnygv svlsnasgnw nwdftsalff astvlsttgy

121 ghtvplsdgg kafciiysvi gipftllflt avvqritvhv trrpvlyfhi rwgfskqvva

181 ivhavllgfv tvscfffipa avfsvleddw nflesfyfcf islstiglgd yvpgegynqk

241 frelykigit cylllgliam Ivvletfcel helkkfrkmf yvkkdkdedq vhiiehdqls

301 fssitdqaag mkedqkqnep fvatqssacv dgpanh

Lysosomal associated membrane protein 3, precursor, NP_055213.2 (SEQ ID NO: 100)

1 mprqlsaaaa Ifaslavilh dgsqmrakaf petrdysqpt aaatvqdikk pvqqpakqap

61 hqtlaarfmd ghitfqtaat vkiptttpat tkntattspi tytlvttqat pnnshtappv

121 tevtvgpsla pyslpptitp pahttgtsss tvshttgntt qpsnqttlpa tlsialhkst

181 tgqkpvqpth apgttaaahn ttrtaapast vpgptlapqp ssvktgiyqv Ingsrlcika

241 emgiqlivqd kesvfsprry fnidpnatqa sgncgtrksn lllnfqggfv nltftkdees

301 yyisevgayl tvsdpetiyq gikhavvmfq tavghsfkcv seqslqlsah Iqvkttdvql

361 qafdfeddhf gnvdecssdy tivlpvigai vvglclmgmg vykirlrcqs sgyqri

MAGE family member B2, NP_002355.2 (SEQ ID NO: 101)

1 mprgqksklr arekrrkard etrglnvpqv teaeeeeapc csssvsggaa ssspaagipq

61 epqrapttaa aaaagvsstk skkgakshqg eknasssqas tstkspsedp Itrksgslvq

121 fllykykikk svtkgemlki vgkrfrehfp eilkkasegl svvfglelnk vnpnghtytf

181 idkvdltdee sllsswdfpr rkllmpllgv iflngnsate eeiweflnml gvydgeehsv

241 fgepwklitk dlvqekyley kqvpssdppr fqflwgpray aetskmkvle flakvngttp

301 cafpthyeea Ikdeekagv

Mitogen-activated protein kinase 13, NP_002745.1 (SEQ ID NO: 102)

1 mslirkkgfy kqdvnktawe Ipktyvspth vgsgaygsvc saidkrsgek vaikklsrpf

61 qseifakray rellllkhmq henviglldv ftpasslrnf ydfylvmpfm qtdlqkimgm

121 efseekiqyl vyqmlkglky ihsagvvhrd Ikpgnlavne dcelkildfg larhadaemt

181 gyvvtrwyra pevilswmhy nqtvdiwsvg cimaemltgk tlfkgkdyld qltqilkvtg

241 vpgtefvqkl ndkaaksyiq slpqtprkdf tqlfpraspq aadllekmle Idvdkrltaa

301 qalthpffep frdpeeetea qqpfddsleh ekltvdewkq hiykeivnfs piarkdsrrr

361 sgmkl

Macrophage receptor with collagenous structure, NP_006761.1 (SEQ ID NO: 103)

1 mrnkkilked ellsetqqaa fhqiamepfe invpkpkrrn gvnfslavvv iylilltaga

61 gllvvqvlnl qarlrvlemy flndtlaaed spsfsllqsa hpgehlaqga srlqvlqaql

121 twvrvshehl Iqrvdnftqn pgmfrikgeq gapglqghkg amgmpgapgp pgppaekgak

181 gamgrdgatg psgpqgppgv kgeaglqgpq gapgkqgatg tpgpqgekgs kgdggligpk

241 getgtkgekg dlglpgskgd rgmkgdagvm gppgaqgskg dfgrpgppgl agfpgakgdq

301 gqpglqgvpg ppgavghpga kgepgsagsp graglpgspg spgatglkgs kgdtglqgqq

361 grkgesgvpg pagvkgeqgs pglagpkgap gqagqkgdqg vkgssgeqgv kgekgergen

421 svsvrivgss nrgraevyys gtwgticdde wqnsdaivfc rmlgyskgra lykvgagtgq

481 iwldnvqcrg testlwsctk nswghhdcsh eedagvecsv

Malic enzyme 1, NADP-dependent malic enzyme, NP_002386.1 (SEQ ID NO: 104)

1 mepeaprrrh thqrgylltr nphlnkdlaf tleerqqlni hgllppsfns qeiqvlrvvk

61 nfehlnsdfd rylllmdlqd rneklfyrvl tsdiekfmpi vytptvglac qqyslvfrkp

121 rglfitihdr ghiasvlnaw pedvikaivv tdgerilglg dlgcngmgip vgklalytac

181 ggmnpqeclp vildvgtene ellkdplyig Irqrrvrgse yddfldefme avsskygmnc

241 liqfedfanv nafrllnkyr nqyctfnddi qgtasvavag llaalritkn klsdqtilfq

301 gageaalgia hlivmaleke glpkekaikk iwlvdskgli vkgrasltqe kekfahehee

361 mknleaivqe ikptaligva aiggafseqi Ikdmaafner piifalsnpt skaecsaeqc

421 ykitkgraif asgspfdpvt Ipngqtlypg qgnnsyvfpg valgvvacgl rqitdniflt

481 taeviaqqvs dkhleegrly pplntirdvs Ikiaekivkd ayqektatvy pepqnkeafv

541 rsqmystdyd qilpdcyswp eevqkiqtkv dq

Migration and invasion inhibitory protein, NP_068752.2 (SEQ ID NO: 105)

1 mveaeelaql rllnlellrq Iwvgqdavrr svaraasess lessssynse tpstpetsst 61 slstscprgr ssvwgppdac rgdlrdvars gvaslppakc qhqeslgrpr phsapslgts 121 slrdpepsgr Igdpgpqeaq tprsilaqqs klskprvtfs eesavpkrsw rlrpylgydw 181 iagsldtsss itsqpeaffs klqefretnk eecicshpep qlpglressg sgveedhecv

241 ycyrvnrrlf pvpvdpgtpc rlcrtprdqq gpgtlaqpah vrvsiplsil epphryhihr

301 rksfdasdtl alprhcllgw difppkseks saprnldlws svsaeaqhqk Isgtsspfhp

361 aspmqmlppt ptwsvpqvpr phvprqkp

Matrix metallopeptidase 12, macrophage metalloelastase preproprotein, NP_002417.2 (SEQ ID NO: 106)

1 mkfllilllq atasgalpln sstsleknnv Ifgerylekf ygleinklpv tkmkysgnlm

61 kekiqemqhf Iglkvtgqld tstlemmhap rcgvpdvhhf rempggpvwr khyityrinn

121 ytpdmnredv dyairkafqv wsnvtplkfs kintgmadil vvfargahgd fhafdgkggi

181 lahafgpgsg iggdahfded efwtthsggt nlfltavhei ghslglghss dpkavmfpty

241 kyvdintfrl saddirgiqs lygdpkenqr Ipnpdnsepa Icdpnlsfda vttvgnkiff

301 fkdrffwlkv serpktsvnl isslwptlps gieaayeiea rnqvflfkdd kywlisnlrp

361 epnypksihs fgfpnfvkki daavfnprfy rtyffvdnqy wryderrqmm dpgypklitk

421 nfqgigpkid avfysknkyy yffqgsnqfe ydfllqritk tlksnswfgc

Matrix metallopeptidase 7, matrilysin preproprotein, NP_002414.1 (SEQ ID NO: 107)

1 mrltvlcavc llpgslalpl pqeaggmsel qweqaqdylk rfylydsetk nansleaklk 61 emqkffglpi tgmlnsrvie imqkprcgvp dvaeyslfpn spkwtskvvt yrivsytrdl

121 phitvdrlvs kalnmwgkei plhfrkvvwg tadimigfar gahgdsypfd gpgntlahaf

181 apgtglggda hfdederwtd gsslginfly aathelghsl gmghssdpna vmyptygngd

241 pqnfklsqdd ikgiqklygk rsnsrkk

Myelin protein zero like 1, myelin protein zero-like protein 1 isoform a precursor, NP_003944.1 (SEQ ID NO: 108)

1 maasagagav iaapdsrrwl wsvlaaalgl Itagvsalev ytpkeifvan gtqgkltckf 61 kststtgglt svswsfqpeg adttvsffhy sqgqvylgny ppfkdriswa gdldkkdasi

121 nienmqfihn gtyicdvknp pdivvqpghi rlyvvekenl pvfpvwvvvg ivtavvlglt

181 llismilavl yrrknskrdy tgcstsesls pvkqaprksp sdteglvksl psgshqgpvi

241 yaqldhsggh hsdkinkses vvyadirkn

Myelin protein zero like 1, myelin protein zero-like protein 1 isoform b precursor, NP_078845.3 (SEQ ID NO: 109)

1 maasagagav iaapdsrrwl wsvlaaalgl Itagvsalev ytpkeifvan gtqgkltckf

61 kststtgglt svswsfqpeg adttvsffhy sqgqvylgny ppfkdriswa gdldkkdasi

121 nienmqfihn gtyicdvknp pdivvqpghi rlyvvekenl pvfpvwvvvg ivtavvlglt

181 llismilavl yrrknskrdy tgaqsymhs

Myelin protein zero like 1, myelin protein zero-like protein 1 isoform c precursor, NP_001139663.1 (SEQ ID NO: 110)

1 maasagagav iaapdsrrwl wsvlaaalgl Itagvsalev ytpkeifvan gtqgkltckf 61 kststtgglt svswsfqpeg adttvsgpvi yaqldhsggh hsdkinkses vvyadirkn Macrophage scavenger receptor 1, macrophage scavenger receptor types I and II isoform type 1, NP_619729.1 (SEQ ID NO: 111)

1 meqwdhfhnq qedtdscses vkfdarsmta llppnpknsp slqeklksfk aalialyllv

61 favlipligi vaaqllkwet kncsvsstna nditqsltgk gndseeemrf qevfmehmsn

121 mekriqhild meanlmdteh fqnfsmttdq rfndillqls tlfssvqghg naideisksl

181 islnttlldl qlnienlngk iqentfkqqe eiskleervy nvsaeimamk eeqvhleqei

241 kgevkvlnni tndlrlkdwe hsqtlrnitl iqgppgppge kgdrgptges gprgfpgpig

301 ppglkgdrga igfpgsrglp gyagrpgnsg pkgqkgekgs gntltpftkv rlvggsgphe

361 grveilhsgq wgticddrwe vrvgqvvcrs Igypgvqavh kaahfgqgtg piwlnevfcf

421 gressieeck irqwgtracs hsedagvtct 1

Macrophage scavenger receptor 1, macrophage scavenger receptor types I and II isoform type 2, NP_002436.1 (SEQ ID NO: 112)

1 meqwdhfhnq qedtdscses vkfdarsmta llppnpknsp slqeklksfk aalialyllv

61 favlipligi vaaqllkwet kncsvsstna nditqsltgk gndseeemrf qevfmehmsn

121 mekriqhild meanlmdteh fqnfsmttdq rfndillqls tlfssvqghg naideisksl

181 islnttlldl qlnienlngk iqentfkqqe eiskleervy nvsaeimamk eeqvhleqei

241 kgevkvlnni tndlrlkdwe hsqtlrnitl iqgppgppge kgdrgptges gprgfpgpig

301 ppglkgdrga igfpgsrglp gyagrpgnsg pkgqkgekgs gntlrpvqlt dhiragps

Macrophage scavenger receptor 1, macrophage scavenger receptor types I and II isoform type 3, NP_619730.1 (SEQ ID NO: 113)

1 meqwdhfhnq qedtdscses vkfdarsmta llppnpknsp slqeklksfk aalialyllv 61 favlipligi vaaqllkwet kncsvsstna nditqsltgk gndseeemrf qevfmehmsn

121 mekriqhild meanlmdteh fqnfsmttdq rfndillqls tlfssvqghg naideisksl

181 islnttlldl qlnienlngk iqentfkqqe eiskleervy nvsaeimamk eeqvhleqei

241 kgevkvlnni tndlrlkdwe hsqtlrnitl iqgppgppge kgdrgptges gprgfpgpig

301 ppglkgdrga igfpgsrglp gyagrpgnsg pkgqkgekgs gntlstgpiw Inevfcfgre

361 ssieeckirq wgtracshse dagvtctl

Myoneurin, isoform A, NP_001172047.1 , NP_061127.1 (SEQ ID NO: 114)

1 mqyshhcehl lerlnkqrea gflcdctivi gefqfkahrn vlasfseyfg aiyrstsenn

61 vfldqsqvka dgfqkllefi ytgtlnldsw nvkeihqaad ylkveevvtk ckikmedfaf

121 ianpssteis sitgnielnq qtclltlrdy nnreksevst dliqanpkqg alakkssqtk

181 kkkkafnspk tgqnktvqyp sdilenasve Ifldanklpt pvveqvaqin dnseleltsv

241 ventfpaqdi vhtvtvkrkr gksqpncalk ehsmsniasv kspyeaensg eeldqryska

301 kpmcntcgkv fseasslrrh mrihkgvkpy vchlcgkaft qcnqlkthvr thtgekpykc

361 elcdkgfaqk cqlvfhsrmh hgeekpykcd vcnlqfatss nlkiharkhs gekpyvcdrc

421 gqrfaqastl tyhvrrhtge kpyvcdtcgk afavssslit hsrkhtgekp yicgicgksf

481 issgelnkhf rshtgerpfi celcgnsytd iknlkkhktk vhsgadktld ssaedhtlse

541 qdsiqkspls etmdvkpsdm tlplalplgt edhhmllpvt dtqsptsdtl Irstvngyse

601 pqliflqqly

Myoneurin, isoform B, NP_001172048.1 (SEQ ID NO: 115)

1 mqyshhcehl lerlnkqrea gflcdctivi gefqfkahrn vlasfseyfg aiyrstsenn

61 vfldqsqvka dgfqkllefi ytgtlnldsw nvkeihqaad ylkveevvtk ckikmedfaf

121 ianpssteis sitgnielnq qtclltlrdy nnreksevst dliqanpkqg alakkssqtk

181 kkkkafnspk tgqnktvqyp sdilenasve Ifldanklpt pvveqvaqin dnseleltsv

241 ventfpaqdi vhtvtvkrkr gksqpncalk ehsmsniasv kspyeaensg eeldqryska

301 kpmcntcgkv fseasslrrh mrihkgvkpy vchlcgkaft qcnqlkthvr thtgekpykc

361 elcdkgfaqk cqlvfhsrmh hgeekpykcd vcnlqfatss nlkiharkhs gekpyvcdrc

421 gqrfaqastl tyhvrrhtge kpyvcdtcgk afavssslit hsrkhtgekp yicgicgksf

481 issgelnkhf rshtgadktl dssaedhtls eqdsiqkspl setmdvkpsd mtlplalplg

541 tedhhmllpv tdtqsptsdt llrstvngys epqliflqql y

N-acetylglucosamine kinase, isoform 1, NP_060037.3 (SEQ ID NO: 116)

1 mrtrtgsqla arevtgsgav prqlegrrcq agrdanggts sdgsssmaai yggvegggtr

61 sevllvsedg kilaeadgls tnhwligtdk cverinemvn rakrkagvdp Ivplrslgls

121 Isggdqedag rilieelrdr fpylsesyli ttdaagsiat atpdggvvli sgtgsncrli

181 npdgsesgcg gwghmmgdeg saywiahqav kivfdsidnl eaaphdigyv kqamfhyfqv

241 pdrlgilthl yrdfdkcrfa gfcrkiaega qqgdplsryi frkagemlgr hivavlpeid

301 pvlfqgkigl pilcvgsvwk swellkegfl laltqgreiq aqnffssftl mklrhssalg

361 gaslgarhig hllpmdysan aiafysytfs

N-acetylglucosamine kinase, isoform 2, NP_001317354.1 , NP_001317355.1 (SEQ ID NO: 117)

1 mvnrakrkag vdplvplrsl glslsggdqe dagrilieel rdrfpylses ylittdaags

61 iatatpdggv vlisgtgsnc rlinpdgses gcggwghmmg degsaywiah qavkivfdsi

121 dnleaaphdi gyvkqamfhy fqvpdrlgil thlyrdfdkc rfagfcrkia egaqqgdpls

181 ryifrkagem Igrhivavlp eidpvlfqgk iglpilcvgs vwkswellke gfllaltqgr

241 eiqaqnffss ftlmklrhss alggaslgar highllpmdy sanaiafysy tfs

Napsin A aspartic peptidase, preproprotein, NP_004842.1 (SEQ ID NO: 118)

1 mspppllqpl llllpllnve psgatlirip Ihrvqpgrri Inllrgwrep aelpklgaps

61 pgdkpifvpl snyrdvqyfg eiglgtppqn ftvafdtgss nlwvpsrrch ffsvpcwlhh

121 rfdpkasssf qangtkfaiq ygtgrvdgil sedkltiggi kgasvifgea Iwepslvfaf

181 ahfdgilglg fpilsvegvr ppmdvlveqg lldkpvfsfy Inrdpeepdg gelvlggsdp

241 ahyippltfv pvtvpaywqi hmervkvgpg Itlcakgcaa ildtgtslit gpteeiralh

301 aaiggiplla geyiilcsei pklpavsfll ggvwfnltah dyviqttrng vrlclsgfqa

361 Idvpppagpf wilgdvflgt yvavfdrgdm kssarvglar artrgadlgw getaqaqfpg

Nuclear transcription factor Y subunit gamma, isoform 1, NP_001136060.1 (SEQ ID NO: 119)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqttp vtmqvgegqq vqivqaqpqg qaqqaqsgtg qtmqvmqqii tntgeiqqip

241 vqlnagqlqy irlaqpvsgt qvvqgqiqtl atnaqqgqrn asqgkprrcl ketlqitqte

301 vqqgqqqfsq ftdgqqlyqi qqvtmpagqd laqpmfiqsa nqpsdgqapq vtgd Nuclear transcription factor Y subunit gamma, isoform 2, NP_055038.2 (SEQ

ID NO: 120)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqttp vtmqvgegqq vqivqaqpqg qaqqaqsgtg qtmqvmqqii tntgeiqqip

241 vqlnagqlqy irlaqpvsgt qvvqgqiqtl atnaqqitqt evqqgqqqfs qftdgqqlyq

301 iqqvtmpagq dlaqpmfiqs anqpsdgqap qvtgd

Nuclear transcription factor Y subunit gamma, isoform 3, NP_001136059.1 (SEQ ID NO: 121)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqttp vtmqvgegqq vqivqaqpqg qaqqaqsgtg qtmqvmqqii tntgeiqqip

241 vqlnagqlqy irlaqpvsgt qvvqgqiqtl atnaqqitqt evqqgqqqfs qftdgqlyqi

301 qqvtmpagqd laqpmfiqsa nqpsdgqapq vtgd

Nuclear transcription factor Y subunit gamma, isoform 4, NP_001136061.1 (SEQ ID NO: 122)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkr

61 ndiamaitkf dqfdflidiv prdelkppkr qeevrqsvtp aepvqyyftl aqqptavqvq

121 gqqqgqqtts stttiqpgqi iiaqpqqgqt tpvtmqvgeg qqvqivqaqp qgqaqqaqsg

181 tgqtmqvmqq iitntgeiqq ipvqlnagql qyirlaqpvs gtqvvqgqiq tlatnaqqit

241 qtevqqgqqq fsqftdgqql yqiqqvtmpa gqdlaqpmfi qsanqpsdgq apqvtgd

Nuclear transcription factor Y subunit gamma, isoform 5, NP_001136062.1

(SEQ ID NO: 123)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqtmq vmqqiitntg eiqqipvqln agqlqyirla qpvsgtqvvq gqiqtlatna

241 qqitqtevqq gqqqfsqftd gqqlyqiqqv tmpagqdlaq pmfiqsanqp sdgqapqvtg

301 d

Nuclear transcription factor Y subunit gamma, isoform 6, NP_001295043.1 (SEQ ID NO: 124)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqttp vtmqvgegqq vqivqaqpqg qaqqaqsgtg qtmqvmqqii tntgeiqqip

241 vqlnagqlqy irlaqpvsgt qvvqgqiqtl atnaqqgqrn asqgkprrcl ketlqitqte

301 vqqgqqqfsq ftdgqrnsvq qarvseltge aeprevkatg nstpctsslp tthppshrag

361 ascvccsqpq qsstspppsd alqwvvvevs gtpnqlethr elhaplpgmt slsplhpsqq

421 lyqiqqvtmp agqdlaqpmf iqsanqpsdg qapqvtgd

Nuclear transcription factor Y subunit gamma, isoform 7, NP_001295044.1 (SEQ ID NO: 125)

1 msteggfggt sssdaqqslq sfwprvmeei rnltvkdfrv qelplarikk imkldedvkm

61 isaeapvlfa kaaqifitel tlrawihted nkrrtlqrnd iamaitkfdq fdflidivpr

121 delkppkrqe evrqsvtpae pvqyyftlaq qptavqvqgq qqgqqttsst ttiqpgqiii

181 aqpqqgqttp vtmqvgegqq vqivqaqpqg qaqqaqsgtg qtmqvmqqii tntgeiqqip

241 vqlnagqlqy irlaqpvsgt qvvqgqiqtl atnaqqitqt evqqgqqqfs qftdgqrnsv

301 qqarvseltg eaeprevkat gnstpctssl ptthppshra gascvccsqp qqsstsppps

361 dalqwvvvev sgtpnqleth relhaplpgm tslsplhpsq qlyqiqqvtm pagqdlaqpm

421 fiqsanqpsd gqapqvtgd

NFKB repressing factor, isoform 1, NP_001166958.1 (SEQ ID NO: 126)

1 mgfmlplifr ysprlmekil qmaegidige mpsydlvlsk pskgqkrhls tcdgqnppkk

61 qagskfharp rfepvhfvas sskderqedp ygpqtkevne qthfasmprd iyqdytqdsf

121 siqdgnsqyc dssgfiltkd qpvtanmyfd sgnpapstts qqansqstpe pspsqtfpes

181 vvaekqyfie kltatiwknl snpemtsgsd kinytymltr ciqacktnpe yiyaplkeip

241 padipknkkl ltdgyacevr cqniylttgy agskngsrdr atelavkllq krievrvvrr

301 kfkhtfgedl vvcqigmssy efppalkppe dlvvlgkdas gqpifnasak hwtnfviten

361 andaigilnn sasfnkmsie ykyemmpnrt wrcrvflqdh claegygtkk tskhaaadea

421 Ikilqktqpt ypsvkssqch tgssprgsgk kkdikdlvvy enssnpvctl ndtaqfnrmt

481 veyvyermtg Irwkckvile seviaeavgv kktvkyeaag eavktlkktq ptvinnlkkg 541 avedvisrne iqgrsaeeay kqqikednig nqllrkmgwt ggglgksgeg irepisvkeq 601 hkreglgldv ervnkiakrd ieqiirnyar seshtdltfs reltnderkq ihqiaqkygl 661 kskshgvghd rylvvgrkrr kedlldqlkq egqvghyelv mpqan

NFKB repressing factor, isoform 2, NP_001166959.1, NP_060014.2 (SEQ ID NO: 127)

1 mekilqmaeg idigempsyd Ivlskpskgq krhlstcdgq nppkkqagsk fharprfepv

61 hfvassskde rqedpygpqt kevneqthfa smprdiyqdy tqdsfsiqdg nsqycdssgf

121 iltkdqpvta nmyfdsgnpa psttsqqans qstpepspsq tfpesvvaek qyfiekltat

181 iwknlsnpem tsgsdkinyt ymltrciqac ktnpeyiyap Ikeippadip knkklltdgy

241 acevrcqniy Ittgyagskn gsrdratela vkllqkriev rvvrrkfkht fgedlvvcqi

301 gmssyefppa Ikppedlvvl gkdasgqpif nasakhwtnf vitenandai gilnnsasfn

361 kmsieykyem mpnrtwrcrv flqdhclaeg ygtkktskha aadealkilq ktqptypsvk

421 ssqchtgssp rgsgkkkdik dlvvyenssn pvctlndtaq fnrmtveyvy ermtglrwkc

481 kvilesevia eavgvkktvk yeaageavkt Ikktqptvin nlkkgavedv isrneiqgrs

541 aeeaykqqik ednignqllr kmgwtggglg ksgegirepi svkeqhkreg Igldvervnk

601 iakrdieqii rnyarsesht dltfsreltn derkqihqia qkyglksksh gvghdrylvv

661 grkrrkedll dqlkqegqvg hyelvmpqan

Plasminogen activator, urokinase, urokinase-type plasminogen activator isoform 1 preproprotein, NP_002649.1 (SEQ ID NO: 128)

1 mrallarlll cvlvvsdskg snelhqvpsn cdclnggtcv snkyfsnihw cncpkkfggq

61 hceidksktc yegnghfyrg kastdtmgrp clpwnsatvl qqtyhahrsd alqlglgkhn

121 ycrnpdnrrr pwcyvqvglk plvqecmvhd cadgkkpssp peelkfqcgq ktlrprfkii

181 ggefttienq pwfaaiyrrh rggsvtyvcg gslispcwvi sathcfidyp kkedyivylg

241 rsrlnsntqg emkfevenli Ihkdysadtl ahhndiallk irskegrcaq psrtiqticl

301 psmyndpqfg tsceitgfgk enstdylype qlkmtvvkli shrecqqphy ygsevttkml

361 caadpqwktd scqgdsggpl vcslqgrmtl tgivswgrgc alkdkpgvyt rvshflpwir

421 shtkeengla 1

Plasminogen activator, urokinase, urokinase-type plasminogen activator isoform 2, NP_001138503.1 (SEQ ID NO: 129)

1 mvfhlrtrye qancdclngg tcvsnkyfsn ihwcncpkkf ggqhceidks ktcyegnghf

61 yrgkastdtm grpclpwnsa tvlqqtyhah rsdalqlglg khnycrnpdn rrrpwcyvqv

121 glkplvqecm vhdcadgkkp ssppeelkfq cgqktlrprf kiiggeftti enqpwfaaiy

181 rrhrggsvty vcggslispc wvisathcfi dypkkedyiv ylgrsrlnsn tqgemkfeve

241 nlilhkdysa dtlahhndia llkirskegr caqpsrtiqt iclpsmyndp qfgtsceitg

301 fgkenstdyl ypeqlkmtvv klishrecqq phyygsevtt kmlcaadpqw ktdscqgdsg

361 gplvcslqgr mtltgivswg rgcalkdkpg vytrvshflp wirshtkeen glal

Plasminogen activator, urokinase, urokinase-type plasminogen activator isoform 3, NP_001306120.1 (SEQ ID NO: 130)

1 mgrpclpwns atvlqqtyha hrsdalqlgl gkhnycrnpd nrrrpwcyvq vglkplvqec

61 mvhdcadgkk pssppeelkf qcgqktlrpr fkiiggeftt ienqpwfaai yrrhrggsvt

121 yvcggslisp cwvisathcf idypkkedyi vylgrsrlns ntqgemkfev enlilhkdys

181 adtlahhndi allkirskeg rcaqpsrtiq ticlpsmynd pqfgtsceit gfgkenstdy

241 lypeqlkmtv vklishrecq qphyygsevt tkmlcaadpq wktdscqgds ggplvcslqg

301 rmtltgivsw grgcalkdkp gvytrvshfl pwirshtkee nglal

Receptor tyrosine kinase like orphan receptor 1, inactive tyrosine-protein kinase transmembrane receptor ROR1 isoform 1 precursor, NP_005003.2 (SEQ ID NO: 131)

1 mhrprrrgtr ppllallaal llaargaaaq etelsvsael vptsswniss elnkdsyltl

61 depmnnitts Igqtaelhck vsgnppptir wfkndapvvq eprrlsfrst iygsrlrirn

121 Idttdtgyfq cvatngkevv sstgvlfvkf gppptaspgy sdeyeedgfc qpyrgiacar

181 fignrtvyme slhmqgeien qitaaftmig tsshlsdkcs qfaipslchy afpycdetss

241 vpkprdlcrd eceilenvlc qteyifarsn pmilmrlklp ncedlpqpes peaancirig

301 ipmadpinkn hkcynstgvd yrgtvsvtks grqcqpwnsq yphthtftal rfpelngghs

361 ycrnpgnqke apwcftlden fksdlcdipa cdskdskekn kmeilyilvp svaiplaial

421 Iffficvcrn nqksssapvq rqpkhvrgqn vemsmlnayk pkskakelpl savrfmeelg

481 ecafgkiykg hlylpgmdha qlvaiktlkd ynnpqqwtef qqeaslmael hhpnivcllg

541 avtqeqpvcm Ifeyinqgdl heflimrsph sdvgcssded gtvkssldhg dflhiaiqia

601 agmeylsshf fvhkdlaarn iligeqlhvk isdlglsrei ysadyyrvqs ksllpirwmp

661 peaimygkfs sdsdiwsfgv vlweifsfgl qpyygfsnqe viemvrkrql Ipcsedcppr

721 myslmtecwn eipsrrprfk dihvrlrswe glsshtsstt psggnattqt tslsaspvsn

781 Isnprypnym fpsqgitpqg qiagfigppi pqnqrfipin gypippgyaa fpaahyqptg 841 pprviqhcpp pksrspssas gststghvts Ipssgsnqea nipllphmsi pnhpggmgit 901 vfgnksqkpy kidskqasll gdanihghte smisael

Receptor tyrosine kinase like orphan receptor 1, inactive tyrosine-protein kinase transmembrane receptor ROR1 isoform 2 precursor, NP_001077061.1 (SEQ ID NO: 132)

1 mhrprrrgtr ppllallaal llaargaaaq etelsvsael vptsswniss elnkdsyltl

61 depmnnitts Igqtaelhck vsgnppptir wfkndapvvq eprrlsfrst iygsrlrirn

121 Idttdtgyfq cvatngkevv sstgvlfvkf gppptaspgy sdeyeedgfc qpyrgiacar

181 fignrtvyme slhmqgeien qitaaftmig tsshlsdkcs qfaipslchy afpycdetss

241 vpkprdlcrd eceilenvlc qteyifarsn pmilmrlklp ncedlpqpes peaancirig

301 ipmadpinkn hkcynstgvd yrgtvsvtks grqcqpwnsq yphthtftal rfpelngghs

361 ycrnpgnqke apwcftlden fksdlcdipa cgk

Runt related transcription factor 1, runt-related transcription factor 1 isoform AMLla, NP_001116079.1 (SEQ ID NO: 133)

1 mripvdasts rrftppstal spgkmsealp Igapdagaal agklrsgdrs mvevladhpg

61 elvrtdspnf Icsvlpthwr cnktlpiafk vvalgdvpdg tlvtvmagnd enysaelrna

121 taamknqvar fndlrfvgrs grgksftlti tvftnppqva tyhraikitv dgpreprrhr

181 qklddqtkpg slsfserlse leqlrrtamr vsphhpaptp npraslnhst afnpqpqsqm

241 qeedtapwrc

Runt related transcription factor 1, runt-related transcription factor 1 isoform AMLlb, NP_001001890.1 (SEQ ID NO: 134)

1 mripvdasts rrftppstal spgkmsealp Igapdagaal agklrsgdrs mvevladhpg

61 elvrtdspnf Icsvlpthwr cnktlpiafk vvalgdvpdg tlvtvmagnd enysaelrna

121 taamknqvar fndlrfvgrs grgksftlti tvftnppqva tyhraikitv dgpreprrhr

181 qklddqtkpg slsfserlse leqlrrtamr vsphhpaptp npraslnhst afnpqpqsqm

241 qdtrqiqpsp pwsydqsyqy Igsiaspsvh patpispgra sgmttlsael ssrlstapdl

301 tafsdprqfp alpsisdprm hypgaftysp tpvtsgigig msamgsatry htylpppypg

361 ssqaqggpfq asspsyhlyy gasagsyqfs mvggersppr ilppctnast gsallnpslp

421 nqsdvveaeg shsnsptnma psarleeavw rpy

Runt related transcription factor 1, runt-related transcription factor 1 isoform AMLlc, NP_001745.2 (SEQ ID NO: 135)

1 masdsifesf psypqcfmre cilgmnpsrd vhdastsrrf tppstalspg kmsealplga

61 pdagaalagk Irsgdrsmve vladhpgelv rtdspnflcs vlpthwrcnk tlpiafkvva

121 Igdvpdgtlv tvmagndeny saelrnataa mknqvarfnd Irfvgrsgrg ksftltitvf

181 tnppqvatyh raikitvdgp reprrhrqkl ddqtkpgsls fserlseleq Irrtamrvsp

241 hhpaptpnpr aslnhstafn pqpqsqmqdt rqiqpsppws ydqsyqylgs iaspsvhpat

301 pispgrasgm ttlsaelssr Istapdltaf sdprqfpalp sisdprmhyp gaftysptpv

361 tsgigigmsa mgsatryhty Ipppypgssq aqggpfqass psyhlyygas agsyqfsmvg

421 gerspprilp pctnastgsa llnpslpnqs dvveaegshs nsptnmapsa rleeavwrpy

Surfactant protein Al, pulmonary surfactant-associated protein Al isoform 1 precursor, NP_001158116.1 , NP_001158119.1, NP_005402.3 (SEQ ID NO: 136)

1 mwlcplalnl ilmaasgavc evkdvcvgsp gipgtpgshg Ipgrdgrdgl kgdpgppgpm

61 gppgempcpp gndglpgapg ipgecgekge pgergppglp ahldeelqat Ihdfrhqilq

121 trgalslqgs imtvgekvfs sngqsitfda iqeacaragg riavprnpee neaiasfvkk

181 yntyayvglt egpspgdfry sdgtpvnytn wyrgepagrg keqcvemytd gqwndrncly

241 srlticef

Surfactant protein Al, pulmonary surfactant-associated protein Al isoform 2 precursor, NP_001087239.2 (SEQ ID NO: 137)

1 mrpcqvpgaa tgpramwlcp lalnlilmaa sgavcevkdv cvgspgipgt pgshglpgrd

61 grdglkgdpg ppgpmgppge mpcppgndgl pgapgipgec gekgepgerg ppglpahlde

121 elqatlhdfr hqilqtrgal slqgsimtvg ekvfssngqs itfdaiqeac araggriavp

181 rnpeeneaia sfvkkyntya yvgltegpsp gdfrysdgtp vnytnwyrge pagrgkeqcv

241 emytdgqwnd rnclysrlti cef

Surfactant protein Al, pulmonary surfactant-associated protein Al isoform 3 precursor, NP_001158117.1 (SEQ ID NO: 138)

1 mrpcqvpgaa tgpramwlcp lalnlilmaa sgavcevkdv cvgtpgipge cgekgepger

61 gppglpahld eelqatlhdf rhqilqtrga Islqgsimtv gekvfssngq sitfdaiqea 121 caraggriav prnpeeneai asfvkkynty ayvgltegps pgdfrysdgt pvnytnwyrg 181 epagrgkeqc vemytdgqwn drnclysrlt icef

Surfactant protein Al, pulmonary surfactant-associated protein Al isoform 4 precursor, NP_001158118.1 (SEQ ID NO: 139) 1 mwlcplalnl ilmaasgavc evkdvcvgtp gipgecgekg epgergppgl pahldeelqa

61 tlhdfrhqil qtrgalslqg simtvgekvf ssngqsitfd aiqeacarag griavprnpe

121 eneaiasfvk kyntyayvgl tegpspgdfr ysdgtpvnyt nwyrgepagr gkeqcvemyt

181 dgqwndrncl ysrlticef

Surfactant protein A2, pulmonary surfactant-associated protein A2 isoform 1 precursor, NP_001092138.1, NP_001307742.1 (SEQ ID NO: 140)

1 mwlcplaltl ilmaasgaac evkdvcvgsp gipgtpgshg Ipgrdgrdgv kgdpgppgpm

61 gppgetpcpp gnnglpgapg vpgergekge agergppglp ahldeelqat Ihdfrhqilq

121 trgalslqgs imtvgekvfs sngqsitfda iqeacaragg riavprnpee neaiasfvkk

181 yntyayvglt egpspgdfry sdgtpvnytn wyrgepagrg keqcvemytd gqwndrncly

241 srlticef

Surfactant protein A2, pulmonary surfactant-associated protein A2 isoform 2 precursor, NP_001307743.1 (SEQ ID NO: 141)

1 mpgaatgpra mwlcplaltl ilmaasgaac evkdvcvgsp gipgtpgshg Ipgrdgrdgv

61 kgdpgppgpm gppgetpcpp gnnglpgapg vpgergekge agergppglp ahldeelqat

121 Ihdfrhqilq trgalslqgs imtvgekvfs sngqsitfda iqeacaragg riavprnpee

181 neaiasfvkk yntyayvglt egpspgdfry sdgtpvnytn wyrgepagrg keqcvemytd

241 gqwndrncly srlticef

Surfactant protein B, pulmonary surfactant-associated protein B precursor, NP_000533.3, NP_942140.2 (SEQ ID NO: 142)

1 mhqagypgcr gamaeshllq wlllllptlc gpgtaawtts slacaqgpef wcqsleqalq

61 cralghclqe vwghvgaddl cqecedivhi Inkmakeaif qdtmrkfleq ecnvlplkll 121 mpqcnqvldd yfplvidyfq nqtdsngicm hlglcksrqp epeqepgmsd plpkplrdpl 181 pdplldklvl pvlpgalqar pgphtqdlse qqfpiplpyc wlcralikri qamipkgala 241 vavaqvcrvv plvaggicqc laerysvill dtllgrmlpq Ivcrlvlrcs mddsagprsp 301 tgewlprdse chlcmsvttq agnsseqaip qamlqacvgs wldrekckqf veqhtpqllt 361 Ivprgwdaht tcqalgvcgt mssplqcihs pdl Surfactant protein C, pulmonary surfactant-associated protein C isoform 1 precursor, NP_001165881.1, NP_003009.2 (SEQ ID NO: 143)

1 mdvgskevlm esppdysaap rgrfgipccp vhlkrllivv vvvvlivvvi vgallmglhm

61 sqkhtemvle msigapeaqq rlalsehlvt tatfsigstg Ivvydyqqll iaykpapgtc

121 cyimkiapes ipslealtrk vhnfqmecsl qakpavptsk Igqaegrdag sapsggdpaf

181 Igmavstlcg evplyyi

Surfactant protein C, pulmonary surfactant-associated protein C isoform 2 precursor, NP_001165828.1 , NP_001304707.1, NP_001304709.1 (SEQ ID NO: 144)

1 mdvgskevlm esppdysaap rgrfgipccp vhlkrllivv vvvvlivvvi vgallmglhm

61 sqkhtemvle msigapeaqq rlalsehlvt tatfsigstg Ivvydyqqll iaykpapgtc 121 cyimkiapes ipslealtrk vhnfqakpav ptsklgqaeg rdagsapsgg dpaflgmavs 181 tlcgevplyy i

Surfactant protein C, pulmonary surfactant-associated protein C isoform 3 precursor, NP_001304708.1 (SEQ ID NO: 145)

1 mdvgskevlm esppvlemsi gapeaqqrla Isehlvttat fsigstglvv ydyqqlliay

61 kpapgtccyi mkiapesips lealtrkvhn fqmecslqak pavptsklgq aegrdagsap

121 sggdpaflgm avstlcgevp lyyi

Surfactant protein D, pulmonary surfactant-associated protein D precursor,

NP_003010.4 (SEQ ID NO: 146)

1 mllfllsalv lltqplgyle aemktyshrt mpsactlvmc ssvesglpgr dgrdgregpr

61 gekgdpglpg aagqagmpgq agpvgpkgdn gsvgepgpkg dtgpsgppgp pgvpgpagre

121 gplgkqgnig pqgkpgpkge agpkgevgap gmqgsagarg lagpkgergv pgergvpgnt

181 gaagsagamg pqgspgargp pglkgdkgip gdkgakgesg Ipdvaslrqq vealqgqvqh

241 Iqaafsqykk velfpngqsv gekifktagf vkpfteaqll ctqaggqlas prsaaenaal

301 qqlvvaknea aflsmtdskt egkftyptge slvysnwapg epnddggsed cveiftngkw

361 ndracgekrl vvcef

Solute carrier family 2 member 5, solute carrier family 2, facilitated glucose transporter member 5 isoform 1, NP_001315548.1, NP_003030.1 (SEQ ID NO: 147)

1 meqqdqsmke grltlvlala tliaafgssf qygynvaavn spallmqqfy netyygrtge

61 fmedfpltll wsvtvsmfpf ggfigsllvg plvnkfgrkg allfnnifsi vpailmgcsr

121 vatsfeliii srllvgicag vssnvvpmyl gelapknlrg algvvpqlfi tvgilvaqif

181 glrnllanvd gwpillgltg vpaalqllll pffpespryl liqkkdeaaa kkalqtlrgw

241 dsvdrevaei rqedeaekaa gfisvlklfr mrslrwqlls iivlmggqql sgvnaiyyya 301 dqiylsagvp eehvqyvtag tgavnvvmtf cavfvvellg rrlllllgfs icliaccvlt

361 aalalqdtvs wmpyisivcv isyvighalg pspipallit eiflqssrps afmvggsvhw

421 Isnftvglif pfiqeglgpy sfivfavicl Ittiyifliv petkaktfie inqiftkmnk

481 vsevypekee Ikelppvtse q

Solute carrier family 2 member 5, solute carrier family 2, facilitated glucose transporter member 5 isoform 2, NP_001129057.1 (SEQ ID NO: 148)

1 meqqdqsmke grltlvlala tliaafgssf qygynvaavn spallmqqfy netyygrtge

61 fmedfpltll wsvtvsmfpf ggfigsllvg plvnkfgrkg allfnnifsi vpailmgcsr

121 vatsfeliii srllvgicag vssnvvpmyl gelapknlrg algvvpqlfi tvgilvaqif

181 glrnllanvd gefrtsrehp hpftttlgpl Ivfqshhhrt glsadwsllt gwmslggpsc

241 pept

Solute carrier family 2 member 5, solute carrier family 2, facilitated glucose transporter member 5 isoform 3, NP_001315549.1 (SEQ ID NO: 149)

1 mgttwllstp qhwtgefmed fpltllwsvt vsmfpfggfi gsllvgplvn kfgrkgallf

61 nnifsivpai Imgcsrvats feliiisrll vgicagvssn vvpmylgela pknlrgalgv

121 vpqlfitvgi Ivaqifglrn llanvdgwpi llgltgvpaa Iqllllpffp esprylliqk

181 kdeaaakkal qtlrgwdsvd revaeirqed eaekaagfis vlklfrmrsl rwqllsiivl

241 mggqqlsgvn aiyyyadqiy Isagvpeehv qyvtagtgav nvvmtfcavf vvellgrrll

301 lllgfsicli accvltaala Iqdtvswmpy isivcvisyv ighalgpspi palliteifl

361 qssrpsafmv ggsvhwlsnf tvglifpfiq eglgpysfiv faviclltti yiflivpetk

421 aktfieinqi ftkmnkvsev ypekeelkel ppvtseq

Solute carrier family 2 member 5, solute carrier family 2, facilitated glucose transporter member 5 isoform 4, NP_001315550.1 (SEQ ID NO: 150)

1 mylgelapkn Irgalgvvpq Ifitvgilva qifglrnlla nvdgwpillg Itgvpaalql

61 lllpffpesp rylliqkkde aaakkalqtl rgwdsvdrev aeirqedeae kaagfisvlk

121 Ifrmrslrwq llsiivlmgg qqlsgvnaiy yyadqiylsa gvpeehvqyv tagtgavnvv

181 mtfcavfvve llgrrlllll gfsicliacc vltaalalqd tvswmpyisi vcvisyvigh

241 algpspipal liteiflqss rpsafmvggs vhwlsnftvg lifpfiqegl gpysfivfav

301 icllttiyif livpetkakt fieinqiftk mnkvsevype keelkelppv tseq

Sperm associated antigen 9, C- Jun-amino-terminal kinase-interacting protein 4 isoform 1, NP_001124000.1 (SEQ ID NO: 151)

1 meledgvvyq eepggsgavm servsglags iyreferlig rydeevvkel mplvvavlen

61 Idsvfaqdqe hqvelellrd dneqlitqye rekalrkhae ekfiefedsq eqekkdlqtr

121 veslesqtrq lelkaknyad qisrleerea elkkeynalh qrhtemihny mehlertklh

181 qlsgsdqles tahsrirker pislgifplp agdglltpda qkggetpgse qwkfqelsqp

241 rshtslkvsn spepqkaveq edelsdvsqg gskattpast ansdvatipt dtplkeeneg

301 fvkvtdapnk seiskhievq vaqetrnvst gsaeneekse vqaiiestpe Idmdkdlsgy

361 kgsstptkgi enkafdrnte slfeelssag sgligdvdeg adllgmgrev enlilentql

421 letknalniv kndliakvde Itcekdvlqg eleavkqakl kleeknrele eelrkaraea

481 edarqkakdd ddsdiptaqr krftrvemar vlmernqyke rlmelqeavr wtemirasre

541 npamqekkrs siwqffsrlf ssssnttkkp eppvnlkyna ptshvtpsvk krsstlsqlp

601 gdkskafdfl seeteaslas rreqkreqyr qvkahvqked grvqafgwsl pqkykqvtng

661 qgenkmknlp vpvylrplde kdtsmklwca vgvnlsggkt rdggsvvgas vfykdvagld

721 tegskqrsas qssldkldqe Ikeqqkelkn qeelsslvwi ctsthsatkv liidavqpgn

781 ildsftvcns hvlciasvpg aretdypage dlsesgqvdk aslcgsmtsn ssaetdsllg

841 gitvvgcsae gvtgaatsps tngaspvmdk ppemeaense vdenvptaee ateategnag

901 saedtvdisq tgvytehvft dplgvqiped Ispvyqssnd sdaykdqisv Ipneqdlvre

961 eaqkmssllp tmwlgaqngc lyvhssvaqw rkclhsiklk dsilsivhvk givlvaladg

1021 tlaifhrgvd gqwdlsnyhl Idlgrphhsi rcmtvvhdkv wcgyrnkiyv vqpkamkiek

1081 sfdahprkes qvrqlawvgd gvwvsirlds tlrlyhahty qhlqdvdiep yvskmlgtgk

1141 Igfsfvrita Imvscnrlwv gtgngviisi pltetnktsg vpgnrpgsvi rvygdensdk

1201 vtpgtfipyc smahaqlcfh ghrdavkffv avpgqvispq ssssgtdltg dkagpsaqep

1261 gsqtplksml visggegyid frmgdegges ellgedlple psvtkaersh livwqvmygn

1321 e

Sperm associated antigen 9, C- Jun-amino-terminal kinase-interacting protein 4 isoform 2, NP_001123999.1 (SEQ ID NO: 152)

1 meledgvvyq eepggsgavm servsglags iyreferlig rydeevvkel mplvvavlen

61 Idsvfaqdqe hqvelellrd dneqlitqye rekalrkhae ekfiefedsq eqekkdlqtr

121 veslesqtrq lelkaknyad qisrleerea elkkeynalh qrhtemihny mehlertklh

181 qlsgsdqles tahsrirker pislgifplp agdglltpda qkggetpgse qwkfqelsqp

241 rshtslkdel sdvsqggska ttpastansd vatiptdtpl keenegfvkv tdapnkseis 301 khievqvaqe trnvstgsae neeksevqai iestpeldmd kdlsgykgss tptkgienka

361 fdrnteslfe elssagsgli gdvdegadll gmgrevenli lentqlletk nalnivkndl

421 iakvdeltce kdvlqgelea vkqaklklee knreleeelr karaeaedar qkakddddsd

481 iptaqrkrft rvemarvlme rnqykerlme Iqeavrwtem irasrenpam qekkrssiwq

541 fvptrfsrlf ssssnttkkp eppvnlkyna ptshvtpsvk krsstlsqlp gdkskafdfl

601 seeteaslas rreqkreqyr qvkahvqked grvqafgwsl pqkykqvtng qgenkmknlp

661 vpvylrplde kdtsmklwca vgvnlsggkt rdggsvvgas vfykdvagld tegskqrsas

721 qssldkldqe Ikeqqkelkn qeelsslvwi ctsthsatkv liidavqpgn ildsftvcns

781 hvlciasvpg aretdypage dlsesgqvdk aslcgsmtsn ssaetdsllg gitvvgcsae

841 gvtgaatsps tngaspvmdk ppemeaense vdenvptaee ateategnag saedtvdisq

901 tgvytehvft dplgvqiped Ispvyqssnd sdaykdqisv Ipneqdlvre eaqkmssllp

961 tmwlgaqngc lyvhssvaqw rkclhsiklk dsilsivhvk givlvaladg tlaifhrgvd

1021 gqwdlsnyhl Idlgrphhsi rcmtvvhdkv wcgyrnkiyv vqpkamkiek sfdahprkes

1081 qvrqlawvgd gvwvsirlds tlrlyhahty qhlqdvdiep yvskmlgtgk Igfsfvrita

1141 Imvscnrlwv gtgngviisi pltetnktsg vpgnrpgsvi rvygdensdk vtpgtfipyc

1201 smahaqlcfh ghrdavkffv avpgqvispq ssssgtdltg dkagpsaqep gsqtplksml

1261 visggegyid frmgdegges ellgedlple psvtkaersh livwqvmygn e

Sperm associated antigen 9, C- Jun-amino-terminal kinase-interacting protein 4 isoform 3, NP_003962.3 (SEQ ID NO: 153)

1 meledgvvyq eepggsgavm servsglags iyreferlig rydeevvkel mplvvavlen

61 Idsvfaqdqe hqvelellrd dneqlitqye rekalrkhae ekfiefedsq eqekkdlqtr

121 veslesqtrq lelkaknyad qisrleerea elkkeynalh qrhtemihny mehlertklh

181 qlsgsdqles tahsrirker pislgifplp agdglltpda qkggetpgse qwkfqelsqp

241 rshtslkdel sdvsqggska ttpastansd vatiptdtpl keenegfvkv tdapnkseis

301 khievqvaqe trnvstgsae neeksevqai iestpeldmd kdlsgykgss tptkgienka

361 fdrnteslfe elssagsgli gdvdegadll gmgrevenli lentqlletk nalnivkndl

421 iakvdeltce kdvlqgelea vkqaklklee knreleeelr karaeaedar qkakddddsd

481 iptaqrkrft rvemarvlme rnqykerlme Iqeavrwtem irasrenpam qekkrssiwq

541 ffsrlfssss nttkkpeppv nlkynaptsh vtpsvkkrss tlsqlpgdks kafdflseet

601 easlasrreq kreqyrqvka hvqkedgrvq afgwslpqky kqvtngqgen kmknlpvpvy

661 Irpldekdts mklwcavgvn Isggktrdgg svvgasvfyk dvagldtegs kqrsasqssl

721 dkldqelkeq qkelknqeel sslvwictst hsatkvliid avqpgnilds ftvcnshvlc

781 iasvpgaret dypagedlse sgqvdkaslc gsmtsnssae tdsllggitv vgcsaegvtg

841 aatspstnga spvmdkppem eaensevden vptaeeatea tegnagsaed tvdisqtgvy

901 tehvftdplg vqipedlspv yqssndsday kdqisvlpne qdlvreeaqk mssllptmwl

961 gaqngclyvh ssvaqwrkcl hsiklkdsil sivhvkgivl valadgtlai fhrgvdgqwd

1021 Isnyhlldlg rphhsircmt vvhdkvwcgy rnkiyvvqpk amkieksfda hprkesqvrq

1081 lawvgdgvwv sirldstlrl yhahtyqhlq dvdiepyvsk mlgtgklgfs fvritalmvs

1141 cnrlwvgtgn gviisiplte tnktsgvpgn rpgsvirvyg densdkvtpg tfipycsmah

1201 aqlcfhghrd avkffvavpg qvispqssss gtdltgdkag psaqepgsqt plksmlvisg

1261 gegyidfrmg deggesellg edlplepsvt kaershlivw qvmygne

Sperm associated antigen 9, C- Jun-amino-terminal kinase-interacting protein 4 isoform 4, NP_001238900.1 (SEQ ID NO: 154)

1 mspgcmllfv fgfvggavvi nsailvslsv lllvhfsist gvpaltqnlp rilrkerpis

61 Igifplpagd glltpdaqkg getpgseqwk fqelsqprsh tslkdelsdv sqggskattp

121 astansdvat iptdtplkee negfvkvtda pnkseiskhi evqvaqetrn vstgsaenee

181 ksevqaiies tpeldmdkdl sgykgsstpt kgienkafdr nteslfeels sagsgligdv

241 degadllgmg revenlilen tqlletknal nivkndliak vdeltcekdv Iqgeleavkq

301 aklkleeknr eleeelrkar aeaedarqka kddddsdipt aqrkrftrve marvlmernq

361 ykerlmelqe avrwtemira srenpamqek krssiwqffs rlfssssntt kkpeppvnlk

421 ynaptshvtp svkkrsstls qlpgdkskaf dflseeteas lasrreqkre qyrqvkahvq

481 kedgrvqafg wslpqkykqv tngqgenkmk nlpvpvylrp Idekdtsmkl wcavgvnlsg

541 gktrdggsvv gasvfykdva gldtegskqr sasqssldkl dqelkeqqke Iknqeelssl

601 vwictsthsa tkvliidavq pgnildsftv cnshvlcias vpgaretdyp agedlsesgq

661 vdkaslcgsm tsnssaetds llggitvvgc saegvtgaat spstngaspv mdkppemeae

721 nsevdenvpt aeeateateg nagsaedtvd isqtgvyteh vftdplgvqi pedlspvyqs

781 sndsdaykdq isvlpneqdl vreeaqkmss llptmwlgaq ngclyvhssv aqwrkclhsi

841 klkdsilsiv hvkgivlval adgtlaifhr gvdgqwdlsn yhlldlgrph hsircmtvvh

901 dkvwcgyrnk iyvvqpkamk ieksfdahpr kesqvrqlaw vgdgvwvsir Idstlrlyha

961 htyqhlqdvd iepyvskmlg tgklgfsfvr italmvscnr Iwvgtgngvi isipltetvi

1021 Ihqgrllglr anktsgvpgn rpgsvirvyg densdkvtpg tfipycsmah aqlcfhghrd 1081 avkffvavpg qvispqssss gtdltgdkag psaqepgsqt plksmlvisg gegyidfrmg 1141 deggesellg edlplepsvt kaershlivw qvmygne

SGT1 homolog, MIS12 kinetochore complex assembly cochaperone, protein SGT1 homolog isoform A, NP_006695.1 (SEQ ID NO: 155)

1 maaaaagtat sqrffqsfsd alidedpqaa leeltkaleq kpddaqyycq raychillgn

61 ycvavadakk slelnpnnst amlrkgicey heknyaaale tftegqklds adanfsvwik

121 rcqeaqngse sevwthqski kydwyqtesq vvitlmiknv qkndvnvefs ekelsalvkl

181 psgedynlkl ellhpiipeq stfkvlstki eiklkkpeav rweklegqgd vptpkqfvad

241 vknlypsssp ytrnwdklvg eikeeeknek legdaalnrl fqqiysdgsd evkramnksf

301 mesggtvlst nwsdvgkrkv einppddmew kky

SGT1 homolog, MIS12 kinetochore complex assembly cochaperone, protein SGT1 homolog isoform B, NP_001124384.1 (SEQ ID NO: 156)

1 maaaaagtat sqrffqsfsd alidedpqaa leeltkaleq kpddaqyycq raychillgn

61 ycvavadakk slelnpnnst amlrkgicey heknyaaale tftegqkldi etgfhrvgqa

121 glqlltssdp paldsqsagi tgadanfsvw ikrcqeaqng sesevwthqs kikydwyqte

181 sqvvitlmik nvqkndvnve fsekelsalv klpsgedynl klellhpiip eqstfkvlst

241 kieiklkkpe avrweklegq gdvptpkqfv advknlypss spytrnwdkl vgeikeeekn

301 eklegdaaln rlfqqiysdg sdevkramnk sfmesggtvl stnwsdvgkr kveinppddm

361 ewkky

SGT1 homolog, MIS12 kinetochore complex assembly cochaperone, protein SGT1 homolog isoform C, NP_001307760.1 (SEQ ID NO: 157)

1 mlsqkevava dakkslelnp nnstamlrkg iceyheknya aaletftegq kldsadanfs

61 vwikrcqeaq ngsesevwth qskikydwyq tesqvvitlm iknvqkndvn vefsekelsa

121 Ivklpsgedy nlklellhpi ipeqstfkvl stkieiklkk peavrwekle gqgdvptpkq

181 fvadvknlyp ssspytrnwd klvgeikeee kneklegdaa Inrlfqqiys dgsdevkram

241 nksfmesggt vlstnwsdvg krkveinppd dmewkky

Sulfotransferase family 10 member 2, sulfotransferase 102 isoform a, NP_001047.1 (SEQ ID NO: 158)

1 maltsdlgkq iklkevegtl Iqpatvdnws qiqsfeakpd dllictypka gttwiqeivd

61 mieqngdvek cqraiiqhrh pfiewarppq psgvekakam psprilkthl stqllppsfw

121 ennckflyva rnakdcmvsy yhfqrmnhml pdpgtweeyf etfingkvvw gswfdhvkgw

181 wemkdrhqil flfyedikrd pkheirkvmq fmgkkvdetv Idkivqetsf ekmkenpmtn

241 rstvsksild qsissfmrkg tvgdwknhft vaqnerfdei yrrkmegtsi nfcmel

Sulfotransferase family 10 member 2, sulfotransferase 102 isoform b, NP_789795.1 (SEQ ID NO: 159)

1 maltsdlgkq iklkevegtl Iqpatvdnws qiqsfeakpd dllictypka gttwiqeivd

61 mieqngdvek cqraiiqhrh pfiewarppq psetgfhhva qaglkllsss nppastsqsa

121 kitdllppsf wennckflyv arnakdcmvs yyhfqrmnhm Ipdpgtweey fetfingkvv

181 wgswfdhvkg wwemkdrhqi Iflfyedikr dpkheirkvm qfmgkkvdet vldkivqets

241 fekmkenpmt nrstvsksil dqsissfmrk gtvgdwknhf tvaqnerfde iyrrkmegts

301 infcmel

Transmembrane protein 52B, isoform 1, NP_694567.1 (SEQ ID NO: 160)

1 mswrpqpcci sscclttdwv hlwyiwllvv igallllcgl tslcfrcccl srqqngedgg

61 pppcevtvia fdhdstlqst itslqsvfgp aarrilavah shsslgqlps sldtlpgyee 121 alhmsrftva mcgqkapdlp pvpeekqlpp tekestrivd swn

Transmembrane protein 52B, isoform 2 precursor, NP_001073283.1 (SEQ ID NO: 161)

1 mgvrvhvvaa sallyfills gtrceencgn pehclttdwv hlwyiwllvv igallllcgl

61 tslcfrcccl srqqngedgg pppcevtvia fdhdstlqst itslqsvfgp aarrilavah

121 shsslgqlps sldtlpgyee alhmsrftva mcgqkapdlp pvpeekqlpp tekestrivd

181 swn

Exportin 7, NP_055839.3 (SEQ ID NO: 162)

1 madhvqslaq lenlckqlye ttdtttrlqa ekalveftns pdclskcqll lergsssysq

61 llaatcltkl vsrtnnplpl eqridirnyv Inylatrpkl atfvtqaliq lyaritklgw

121 fdcqkddyvf rnaitdvtrf Iqdsveycii gvtilsqltn einqadtthp Itkhrkiass

181 frdsslfdif tlscnllkqa sgknlnlnde sqhgllmqll klthnclnfd figtstdess

241 ddlctvqipt swrsafldss tlqlffdlyh sippsfsplv Isclvqiasv rrslfnnaer

301 akflshlvdg vkrilenpqs Isdpnnyhef crllarlksn yqlgelvkve nypevirlia

361 nftvtslqhw efapnsvhyl Islwqrlaas vpyvkateph mletytpevt kayitsrles

421 vhiilrdgle dpledtglvq qqldqlstig rceyektcal Ivqlfdqsaq syqellqsas

481 aspmdiavqe grltwlvyii gaviggrvsf astdeqdamd gelvcrvlql mnltdsrlaq 541 agneklelam Isffeqfrki yigdqvqkss klyrrlsevl glndetmvls vfigkiitnl

601 kywgrcepit sktlqllndl sigyssvrkl vklsavqfml nnhtsehfsf Iginnqsnlt

661 dmrcrttfyt algrllmvdl gededqyeqf mlpltaafea vaqmfstnsf neqeakrtlv

721 glvrdlrgia fafnaktsfm mlfewiypsy mpilqraiel wyhdpacttp vlklmaelvh

781 nrsqrlqfdv sspngillfr etskmitmyg nriltlgevp kdqvyalklk gisicfsmlk

841 aalsgsyvnf gvfrlygdda Idnalqtfik lllsiphsdl Idypklsqsy ysllevltqd

901 hmnfiaslep hvimyilssi segltaldtm vctgccscld hivtylfkql srstkkrttp

961 Inqesdrflh imqqhpemiq qmlstvlnii ifedcrnqws msrpllglil Inekyfsdlr

1021 nsivnsqppe kqqamhlcfe nlmegiernl Itknrdrftq nlsafrrevn dsmknstygv

1081 nsndrams

YES proto-oncogene 1, Src family tyrosine kinase, tyrosine-protein kinase Yes, NP_005424.1 (SEQ ID NO: 163)

1 mgcikskenk spaikyrpen tpepvstsvs hygaepttvs pcpsssakgt avnfsslsmt

61 pfggssgvtp fggasssfsv vpssypaglt ggvtifvaly dyearttedl sfkkgerfqi

121 inntegdwwe arsiatgkng yipsnyvapa dsiqaeewyf gkmgrkdaer lllnpgnqrg

181 iflvresett kgayslsird wdeirgdnvk hykirkldng gyyittraqf dtlqklvkhy

241 tehadglchk Ittvcptvkp qtqglakdaw eipreslrle vklgqgcfge vwmgtwngtt

301 kvaiktlkpg tmmpeaflqe aqimkklrhd klvplyavvs eepiyivtef mskgslldfl

361 kegdgkylkl pqlvdmaaqi adgmayierm nyihrdlraa nilvgenlvc kiadfglarl

421 iedneytarq gakfpikwta peaalygrft iksdvwsfgi Iqtelvtkgr vpypgmvnre

481 vleqvergyr mpcpqgcpes lhelmnicwk kdpderptfe yiqsfledyf tatepqyqpg

541 enl

Coiled-coil domain containing 80, coiled-coil domain-containing 80 precursor, NP_955805.1, NP_955806.1 (SEQ ID NO: 164)

1 mtwrmgprft mllamwlvcg sephphatir gshggrkvpl vspdssrpar flrhtgrsrg

61 ierstleepn Iqplqrrrsv pvlrlarpte pparsdinga avrpeqrpaa rgspremird

121 egssarsrml rfpsgssspn ilasfagknr vwvisaphas egyyrlmmsl Ikddvycela

181 erhiqqivlf hqageeggkv rritsegqil eqpldpslip klmsflklek gkfgmvllkk

241 tlqveerypy pvrleamyev idqgpirrie kirqkgfvqk ckasgvegqv vaegndgggg

301 agrpslgsek kkedprraqv pptresrvkv Irklaatapa Ipqppstpra ttlppapatt

361 vtrstsravt vaarpmttta fpttqrpwtp spshrppttt evitarrpsv senlyppsrk

421 dqhrerpqtt rrpskatsle sftnapptti sepstraagp grfrdnrmdr rehghrdpnv

481 vpgppkpake kppkkkaqdk ilsneyeeky dlsrptasql edelqvgnvp Ikkakeskkh

541 eklekpekek kkkmknenad kllksekqmk ksekkskqek ekskkkkggk teqdgyqkpt

601 nkhftqspkk svadllgsfe gkrrlllita pkaennmyvq qrdeylesfc kmatrkisvi

661 tifgpvnnst mkidhfqldn ekpmrvvdde dlvdqrlise Irkeygmtyn dffmvltdvd

721 Irvkqyyevp itmksvfdli dtfqsrikdm ekqkkegivc kedkkqslen flsrfrwrrr

781 llvisapnde dwaysqqlsa Isgqacnfgl rhitilkllg vgeevggvle Ifpingssvv

841 eredvpahlv kdirnyfqvs peyfsmllvg kdgnvkswyp spmwsmvivy dlidsmqlrr

901 qemaiqqslg mrcpedeyag ygyhsyhqgy qdgyqddyrh hesyhhgypy

Acrosin-binding protein precursor NP_115878.2 (SEQ ID NO: 165)

1 mrkpaagflp sllkvlllpl apaaaqdstq astpgsplsp teyerffall tptwkaettc

61 rlrathgcrn ptlvqldqye nhglvpdgav csnlpyaswf esfcqfthyr csnhvyyakr

121 vlcsqpvsil spntlkeiea saevspttmt spisphftvt erqtfqpwpe rlsnnveell

181 qsslslggqe qapehkqeqg vehrqeptqe hkqeegqkqe eqeeeqeeeg kqeegqgtke

241 greavsqlqt dsepkfhses Issnpssfap rvrevestpm imeniqelir saqeidemne

301 iydensywrn qnpgsllqlp hteallvlcy siventciit ptakawkyme eeilgfgksv

361 cdslgrrhms tcalcdfcsl kleqchseas Iqrqqcdtsh ktpfvsplla sqslsignqv

421 gspesgrfyg Idlygglhmd fwcarlatkg cedvrvsgwl qteflsfqdg dfptkicdtd

481 yiqypnycsf ksqqclmrnr nrkvsrmrcl qnetysalsp gksedvvlrw sqefstltlg

541 qfg

Alpha-fetoprotein, isoform 1 NP_001125.1 (SEQ ID NO: 166)

1 mkwvesifli fllnftesrt Ihrneygias ildsyqctae isladlatif faqfvqeaty

61 kevskmvkda Itaiekptgd eqssgclenq Ipafleelch ekeilekygh sdccsqseeg

121 rhncflahkk ptpasiplfq vpepvtscea yeedretfmn kfiyeiarrh pflyaptill

181 waarydkiip scckaenave cfqtkaatvt kelresslln qhacavmknf gtrtfqaitv

241 tklsqkftkv nfteiqklvl dvahvhehcc rgdvldclqd gekimsyics qqdtlsnkit

301 eccklttler gqciihaend ekpeglspnl nrflgdrdfn qfssgeknif lasfvheysr

361 rhpqlavsvi Irvakgyqel lekcfqtenp lecqdkgeee Iqkyiqesqa lakrscglfq

421 klgeyylqna flvaytkkap qltsselmai trkmaataat ccqlsedkll acgegaadii

481 ighlcirhem tpvnpgvgqc ctssyanrrp cfsslvvdet yvppafsddk fifhkdlcqa 541 qgvalqtmkq eflinlvkqk pqiteeqlea viadfsglle kccqgqeqev cfaeegqkli 601 sktraalgv

Alpha-fetoprotein, isoform 2 NP_001341646.1 (SEQ ID NO: 167)

1 mnkfiyeiar rhpflyapti llwaarydki ipscckaena vecfqtkaat vtkelressl

61 Inqhacavmk nfgtrtfqai tvtklsqkft kvnfteiqkl vldvahvheh ccrgdvldcl

121 qdgerimsyi csqqdtlsnk iteccklttl ergqciihae ndekpeglsp nlnrflgdrd

181 fnqfssgekn iflasfvhey srrhpqlavs vilrvakgyq ellekcfqte nplecqdkge

241 eelqkyiqes qalakrscgl fqklgeyylq naflvaytkk apqltsselm aitrkmaata

301 atccqlsedk llacgegaad iiighlcirh emtpvnpgvg qcctssyanr rpcfsslvvd

361 etyvppafsd dkfifhkdlc qaqgvalqtm kqeflinlvk qkpqiteeql eaviadfsgl

421 lekccqgqeq evcfaeegqk lisktraalg v

Absent in melanoma 1 protein NP_001615.2 (SEQ ID NO: 168)

1 mplsppaqgd pgepspcrpp kkhttfhlwr skkkqqpapp dcgvfvphpl papagearal

61 dvvdgkyvvr dsqefplhcg esqffhttse algslllesg ifkksraqpp ednrrkpvlg

121 klgtlftagr rrnsrngles ptrsnakpls pkdvvaspkl peresersrs qssqlkqtdt

181 seegsprenp reaegelpes ggpaappdae Isprwsssaa avavqqchen dspqleplea

241 egepfpdatt takqlhsspg nssrqenaet parspgedas pgagheqeaf Igvrgapgsp

301 tqerpagglg eapngapsvc aeegslgprn arsqppkgas dlpgeppaeg aahtassaqa

361 dctarpkgha hpakvltldi ylsktegaqv depvvitpra edcgdwddme krssgrrsgr

421 rrgsqkstds pgadaelpes aarddavfdd evapnaasdn asaekkvksp raaldggvas

481 aaspeskpsp gtkgqlrges drskqpppas sptkrkgrsr aleavpappa sgprapakes

541 ppkrvpdpsp vtkgtaaesg eeaaraipre Ipvksssllp eikpehkrgp Ipnhfngrae

601 ggrsrelgra agapgasdad glkprnhfgv grstvttkvt Ipakpkhvel nlktpknlds

661 Ignehnpfsq pvhkgntatk islfenkrtn ssprhtdirg qrntpasskt fvgraklnla

721 kkakemeqpe kkvmpnspqn gvlvketaie tkvtvseeei Ipatrgmngd ssenqalgpq

781 pnqddkadvq tdagclsepv asalipvkdh kllekedsea adskslvlen vtdtaqdipt

841 tvdtkdlppt ampkpqhtfs dsqspaessp gpslslsapa pgdvpkdtcv qspissfpct

901 dlkvsenhkg cvlpvsrqnn ekmpllelgg ettpplster speavgsecp srvlvqvrsf

961 vlpvestqdv ssqvipesse vrevqlptch snepevvsva scappqeevl gnehshctae

1021 laaksgpqvi ppasektlpi qaqsqgsrtp Imaessptns pssgnhlatp qrpdqtvtng

1081 qdspasllni sagsddsvfd sssdmekfte iikqmdsavc mpmkrkkarm pnspaphfam

1141 ppihedhlek vfdpkvftfg Igkkkesqpe mspalhlmqn Idtksklrpk rasaeqsvlf

1201 kslhtntngn seplvmpein dkenrdvtng gikrsrleks alfssllssl pqdkifspsv

1261 tsvntmttaf stsqngslsq ssvsqptteg appcglnkeq snllpdnslk vfnfnsssts

1321 hsslkspshm ekypqkektk edldsrsnlh Ipetkfsels klknddmeka nhiesviksn

1381 Ipncansdtd fmglfkssry dpsisfsgms Isdtmtlrgs vqnklnprpg kvviysepdv

1441 sekcievfsd iqdcsswsls pvilikvvrg cwilyeqpnf eghsipleeg elelsglwgi

1501 edilerheea esdkpvvigs irhvvqdyrv shidlftepe glgilssyfd dteemqgfgv

1561 mqktcsmkvh wgtwliyeep gfqgvpfile pgeypdlsfw dteeayigsm rplkmggrkv

1621 efptdpkvvv yekpffegkc veletgmcsf vmeggeteea tgddhlpfts vgsmkvlrgi

1681 wvayekpgft ghqylleege yrdwkawggy ngelqslrpi Igdfsnahmi myseknfgsk

1741 gssidvlgiv anlketgygv ktqsinvlsg vwvayenpdf tgeqyildkg fytsfedwgg

1801 knckissvqp icldsftgpr rrnqihlfse pqfqghsqsf eettsqidds fstkscrvsg

1861 gswvvydgen ftgnqyvlee ghypclsamg cppgatfksl rfidvefsep tiilferedf

1921 kgkkielnae tvnlrslgfn tqirsvqvig giwvtyeygs yrgrqfllsp aevpnwyefs

1981 gcrqigslrp fvqkriyfrl rnkatglfms tngnledlkl Iriqvmedvg addqiwiyqe

2041 gcikcriaed ccltivgslv tsgsklglal dqnadsqfws Iksdgriysk Ikpnlvldik

2101 ggtqydqnhi ilntvskekf tqvweamvly t

A-kinase anchoring protein 4, isoform 1 NP_003877.2 (SEQ ID NO: 169)

1 mmaysdttmm sddidwlrsh rgvckvdlyn pegqqdqdrk vicfvdvstl nvedkdykda

61 assssegnln Igsleekeii vikdtekkdq sktegsvclf kqapsdpvsv Inwllsdlqk

121 yalgfqhals pststckhkv gdtegeyhra ssencysvya dqvnidylmn rpqnlrlemt

181 aakntnnnqs psappakpps tqravispdg ecsiddlsfy vnrlsslviq mahkeikekl

241 egkskclhhs icpspgnker isprtpaski asemayeave Itaaemrgtg eesreggqks

301 flyselsnks ksgdkqmsqr eskefadsis kglmvyanqv asdmmvslmk tlkvhssgkp

361 ipasvvlkrv llrhtkeivs dlidscmknl hnitgvlmtd sdfvsavkrn Ifnqwkqnat

421 dimeamlkrl vsaligeeke tksqslsyas Ikagshdpkc rnqslefstm kaemkerdkg

481 kmksdpcksl tsaekvgehi Ikegltiwnq kqgnsckvat kacsnkdekg ekinastdsl

541 akdlivsalk liqyhltqqt kgkdtceedc pgstmgymaq stqyekcggg qsakalsvkq

601 leshrapgps tcqkenqhld sqkmdmsniv Imliqkllne npfkcedpce genkcsepra

661 skaasmsnrs dkaeeqcqeh qeldctsgmk qangqfidkl vesvmklcli makysndgaa 721 laeleeqaas ankpnfrgtr cihsgampqn yqdslghevi vnnqcstnsl qkqlqavlqw 781 iaasqfnvpm lyfmgdkdgq leklpqvsak aaekgysvgg llqevmkfak erqpdeavgk 841 varkqlldwl lanl

A-kinase anchoring protein 4, isoform 2 NP_647450.1 (SEQ ID NO: 170)

1 msddidwlrs hrgvckvdly npegqqdqdr kvicfvdvst Invedkdykd aassssegnl

61 nlgsleekei ivikdtekkd qsktegsvcl fkqapsdpvs vlnwllsdlq kyalgfqhal

121 spststckhk vgdtegeyhr assencysvy adqvnidylm nrpqnlrlem taakntnnnq

181 spsappakpp stqravispd gecsiddlsf yvnrlsslvi qmahkeikek legkskclhh

241 sicpspgnke risprtpask iasemayeav eltaaemrgt geesreggqk sflyselsnk

301 sksgdkqmsq reskefadsi skglmvyanq vasdmmvslm ktlkvhssgk pipasvvlkr

361 vllrhtkeiv sdlidscmkn Ihnitgvlmt dsdfvsavkr nlfnqwkqna tdimeamlkr

421 Ivsaligeek etksqslsya slkagshdpk crnqslefst mkaemkerdk gkmksdpcks

481 Itsaekvgeh ilkegltiwn qkqgnsckva tkacsnkdek gekinastds lakdlivsal

541 kliqyhltqq tkgkdtceed cpgstmgyma qstqyekcgg gqsakalsvk qleshrapgp

601 stcqkenqhl dsqkmdmsni vlmliqklln enpfkcedpc egenkcsepr askaasmsnr

661 sdkaeeqcqe hqeldctsgm kqangqfidk Ivesvmklcl imakysndga alaeleeqaa

721 sankpnfrgt rcihsgampq nyqdslghev ivnnqcstns Iqkqlqavlq wiaasqfnvp

781 mlyfmgdkdg qleklpqvsa kaaekgysvg gllqevmkfa kerqpdeavg kvarkqlldw

841 llanl

ALK tryrosine kinase receptor, isoform 1 NP_004295.2 (SEQ ID NO: 171)

1 mgaigllwll plllstaavg sgmgtgqrag spaagpplqp replsysrlq rkslavdfvv

61 pslfrvyard lllppsssel kagrpeargs laldcapllr llgpapgvsw tagspapaea

121 rtlsrvlkgg svrklrrakq Ivlelgeeai legcvgppge aavgllqfnl selfswwirq

181 gegrlrirlm pekkasevgr egrlsaaira sqprllfqif gtghsslesp tnmpspspdy

241 ftwnltwimk dsfpflshrs ryglecsfdf pceleysppl hdlrnqswsw rripseeasq

301 mdlldgpgae rskemprgsf lllntsadsk htilspwmrs ssehctlavs vhrhlqpsgr

361 yiaqllphne aareillmpt pgkhgwtvlq grigrpdnpf rvaleyissg nrslsavdff

421 alkncsegts pgskmalqss ftcwngtvlq Igqacdfhqd caqgedesqm crklpvgfyc

481 nfedgfcgwt qgtlsphtpq wqvrtlkdar fqdhqdhall Isttdvpase satvtsatfp

541 apiksspcel rmswlirgvl rgnvslvlve nktgkeqgrm vwhvaayegl slwqwmvlpl

601 Idvsdrfwlq mvawwgqgsr aivafdnisi sldcyltisg edkilqntap ksrnlfernp

661 nkelkpgens prqtpifdpt vhwlfttcga sgphgptqaq cnnayqnsnl svevgsegpl

721 kgiqiwkvpa tdtysisgyg aaggkggknt mmrshgvsvl gifnlekddm lyilvgqqge

781 dacpstnqli qkvcigennv ieeeirvnrs vhewaggggg gggatyvfkm kdgvpvplii

841 aaggggrayg aktdtfhper lennssvlgl ngnsgaaggg ggwndntsll wagkslqega

901 tgghscpqam kkwgwetrgg fggggggcss ggggggyigg naasnndpem dgedgvsfis

961 plgilytpal kvmeghgevn ikhylncshc evdechmdpe shkvicfcdh gtvlaedgvs

1021 civsptpeph Iplslilsvv tsalvaalvl afsgimivyr rkhqelqamq melqspeykl

1081 sklrtstimt dynpnycfag ktssisdlke vprknitlir glghgafgev yegqvsgmpn

1141 dpsplqvavk tlpevcseqd eldflmeali iskfnhqniv rcigvslqsl prfillelma

1201 ggdlksflre trprpsqpss lamldllhva rdiacgcqyl eenhfihrdi aarnclltcp

1261 gpgrvakigd fgmardiyra syyrkggcam Ipvkwmppea fmegiftskt dtwsfgvllw

1321 eifslgympy psksnqevle fvtsggrmdp pkncpgpvyr imtqcwqhqp edrpnfaiil

1381 erieyctqdp dvintalpie ygplveeeek vpvrpkdpeg vppllvsqqa kreeerspaa

1441 ppplpttssg kaakkptaae isvrvprgpa vegghvnmaf sqsnppselh kvhgsrnkpt

1501 slwnptygsw ftekptkknn piakkephdr gnlglegsct vppnvatgrl pgasllleps

1561 sltanmkevp Ifrlrhfpcg nvnygyqqqg Ipleaatapg aghyedtilk sknsmnqpgp

ALK tyrosin kinese receptor, isoform 2 NP_001340694.1 (SEQ ID NO: 172)

1 mqmelqspey klsklrtsti mtdynpnycf agktssisdl kevprknitl irglghgafg

61 evyegqvsgm pndpsplqva vktlpevcse qdeldflmea liiskfnhqn ivrcigvslq

121 slprfillel maggdlksfl retrprpsqp sslamldllh vardiacgcq yleenhfihr

181 diaarncllt cpgpgrvaki gdfgmardiy rasyyrkggc amlpvkwmpp eafmegifts

241 ktdtwsfgvl Iweifslgym pypsksnqev lefvtsggrm dppkncpgpv yrimtqcwqh

301 qpedrpnfai ilerieyctq dpdvintalp ieygplveee ekvpvrpkdp egvppllvsq

361 qakreeersp aappplptts sgkaakkpta aeisvrvprg pavegghvnm afsqsnppse

421 Ihkvhgsrnk ptslwnptyg swftekptkk nnpiakkeph drgnlglegs ctvppnvatg

481 rlpgasllle pssltanmke vplfrlrhfp cgnvnygyqq qglpleaata pgaghyedti

541 Iksknsmnqp gp

Angiopoietin-2 , isoform a NP_001138.1 (SEQ ID NO: 173)

1 mwqivfftls cdlvlaaayn nfrksmdsig kkqyqvqhgs csytfllpem dncrsssspy 61 vsnavqrdap leyddsvqrl qvlenimenn tqwlmkleny iqdnmkkemv eiqqnavqnq 121 tavmieigtn llnqtaeqtr kltdveaqvl nqttrlelql lehslstnkl ekqildqtse

181 inklqdknsf lekkvlamed khiiqlqsik eekdqlqvlv skqnsiieel ekkivtatvn

241 nsvlqkqqhd Imetvnnllt mmstsnsakd ptvakeeqis frdcaevfks ghttngiytl

301 tfpnsteeik aycdmeaggg gwtiiqrred gsvdfqrtwk eykvgfgnps geywlgnefv

361 sqltnqqryv Ikihlkdweg neayslyehf ylsseelnyr ihlkgltgta gkissisqpg

421 ndfstkdgdn dkcickcsqm Itggwwfdac gpsnlngmyy pqrqntnkfn gikwyywkgs

481 gyslkattmm irpadf

Angiopoietin-2 , isoform b NP_001112359.1 (SEQ ID NO: 174)

1 mwqivfftls cdlvlaaayn nfrksmdsig kkqyqvqhgs csytfllpem dncrsssspy

61 vsnavqrdap leyddsvqrl qvlenimenn tqwlmkleny iqdnmkkemv eiqqnavqnq

121 tavmieigtn llnqtaeqtr kltdveaqvl nqttrlelql lehslstnkl ekqildqtse

181 inklqdknsf lekkvlamed khiiqlqsik eekdqlqvlv skqnsiieel ekkivtatvn

241 nsvlqkqqhd Imetvnnllt mmstsnskdp tvakeeqisf rdcaevfksg httngiytlt

301 fpnsteeika ycdmeagggg wtiiqrredg svdfqrtwke ykvgfgnpsg eywlgnefvs

361 qltnqqryvl kihlkdwegn eayslyehfy Isseelnyri hlkgltgtag kissisqpgn

421 dfstkdgdnd kcickcsqml tggwwfdacg psnlngmyyp qrqntnkfng ikwyywkgsg

481 yslkattmmi rpadf

Angiopoietin-2, isoform c NP_001112360.1 (SEQ ID NO: 175)

1 mwqivfftls cdlvlaaayn nfrksmdsig kkqyqvqhgs csytfllpem dncrsssspy

61 vsnavqrdap leyddsvqrl qvlenimenn tqwlmkvlnq ttrlelqlle hslstnklek

121 qildqtsein klqdknsfle kkvlamedkh iiqlqsikee kdqlqvlvsk qnsiieelek

181 kivtatvnns vlqkqqhdlm etvnnlltmm stsnsakdpt vakeeqisfr dcaevfksgh

241 ttngiytltf pnsteeikay cdmeaggggw tiiqrredgs vdfqrtwkey kvgfgnpsge

301 ywlgnefvsq Itnqqryvlk ihlkdwegne ayslyehfyl sseelnyrih Ikgltgtagk

361 issisqpgnd fstkdgdndk cickcsqmlt ggwwfdacgp snlngmyypq rqntnkfngi

421 kwyywkgsgy slkattmmir padf

Angiopoietin-1 , isoform 1 precursor NP_001137.2 (SEQ ID NO: 176)

1 mtvflsfafl aailthigcs nqrrspensg rrynriqhgq caytfilpeh dgncresttd

61 qyntnalqrd aphvepdfss qklqhlehvm enytqwlqkl enyivenmks emaqiqqnav

121 qnhtatmlei gtsllsqtae qtrkltdvet qvlnqtsrle iqllenslst yklekqllqq

181 tneilkihek nsllehkile megkhkeeld tlkeekenlq glvtrqtyii qelekqlnra

241 ttnnsvlqkq qlelmdtvhn Ivnlctkegv llkggkreee kpfrdcadvy qagfnksgiy

301 tiyinnmpep kkvfcnmdvn gggwtviqhr edgsldfqrg wkeykmgfgn psgeywlgne

361 fifaitsqrq ymlrielmdw egnraysqyd rfhignekqn yrlylkghtg tagkqsslil

421 hgadfstkda dndncmckca Imltggwwfd acgpsnlngm fytagqnhgk Ingikwhyfk

481 gpsyslrstt mmirpldf

Angiopoietin-1, isoform 2 precursor NP_001186788.1 (SEQ ID NO: 177)

1 mtvflsfafl aailthigcs nqrrspensg rrynriqhgq caytfilpeh dgncresttd

61 qyntnalqrd aphvepdfss qklqhlehvm enytqwlqkl enyivenmks emaqiqqnav

121 qnhtatmlei gtsllsqtae qtrkltdvet qvlnqtsrle iqllenslst yklekqllqq

181 tneilkihek nsllehkile megkhkeeld tlkeekenlq glvtrqtyii qelekqlnra

241 ttnnsvlqkq qlelmdtvhn Ivnlctkevl Ikggkreeek pfrdcadvyq agfnksgiyt

301 iyinnmpepk kvfcnmdvng ggwtviqhre dgsldfqrgw keykmgfgnp sgeywlgnef

361 ifaitsqrqy mlrielmdwe gnraysqydr fhignekqny rlylkghtgt agkqsslilh

421 gadfstkdad ndncmckcal mltggwwfda cgpsnlngmf ytagqnhgkl ngikwhyfkg

481 psyslrsttm mirpldf

Angiopoietin-1, isoform 3 precursor NP_001300980.1 (SEQ ID NO: 178)

1 megkhkeeld tlkeekenlq glvtrqtyii qelekqlnra ttnnsvlqkq qlelmdtvhn

61 Ivnlctkegv llkggkreee kpfrdcadvy qagfnksgiy tiyinnmpep kkvfcnmdvn

121 gggwtviqhr edgsldfqrg wkeykmgfgn psgeywlgne fifaitsqrq ymlrielmdw

181 egnraysqyd rfhignekqn yrlylkghtg tagkqsslil hgadfstkda dndncmckca

241 Imltggwwfd acgpsnlngm fytagqnhgk Ingikwhyfk gpsyslrstt mmirpldf

Ankyrin repeat domain-containing protein 30A NP_443723.2 (SEQ ID NO: 179)

1 mtkrkktinl niqdaqkrta Ihwacvnghe evvtflvdrk cqldvldgeh rtplmkalqc

61 hqeacanili dsgadinlvd vygntalhya vyseilsvva kllshgavie vhnkasltpl

121 llsitkrseq ivefllikna nanavnkykc talmlavchg sseivgmllq qnvdvfaadi

181 cgvtaehyav tcgfhhiheq imeyirklsk nhqntnpegt sagtpdeaap laertpdtae

241 slvektpdea aplvertpdt aeslvektpd eaaslvegts dkiqclekat sgkfeqsaee

301 tpreitspak etsekftwpa kgrprkiawe kkedtpreim spaketsekf twaakgrprk

361 iawekketpv ktgcvarvts nktkvlekgr skmiacptke sstkasandq rfpseskqee

421 deeyscdsrs Ifessakiqv cipesiyqkv meinreveep pkkpsafkpa iemqnsvpnk 481 afelkneqtl radpmfppes kqkdyeensw dseslcetvs qkdvclpkat hqkeidking

541 kleespnkdg llkatcgmkv siptkalelk dmqtfkaepp gkpsafepat emqksvpnka

601 lelkneqtlr adeilpsesk qkdyeenswd teslcetvsq kdvclpkaah qkeidkingk

661 legspvkdgl Ikancgmkvs iptkalelmd mqtfkaeppe kpsafepaie mqksvpnkal

721 elkneqtlra deilpseskq kdyeesswds eslcetvsqk dvclpkathq keidkingkl

781 eespdndgfl kapcrmkvsi ptkalelmdm qtfkaeppek psafepaiem qksvpnkale

841 Ikneqtlrad qmfpseskqk kveenswdse slretvsqkd vcvpkathqk emdkisgkle

901 dstslskild tvhscerare Iqkdhceqrt gkmeqmkkkf cvlkkklsea keiksqlenq

961 kvkweqelcs vrltlnqeee krrnadilne kireelgrie eqhrkelevk qqleqalriq

1021 dielksvesn Inqvshthen enyllhencm Ikkeiamlkl eiatlkhqyq ekenkyfedi

1081 kilkeknael qmtlklkees Itkrasqysg qlkvliaent mltsklkekq dkeileaeie

1141 shhprlasav qdhdqivtsr ksqepafhia gdaclqrkmn vdvsstiynn evlhqplsea

1201 qrkskslkin Inyagdalre ntlvsehaqr dqretqcqmk eaehmyqneq dnvnkhteqq

1261 esldqklfql qsknmwlqqq Ivhahkkadn kskitidihf lerkmqhhll kekneeifny

1321 nnhlknriyq yekekaeten s

Androgen receptor, isoform 1 NP_000035.2 (SEQ ID NO: 180)

1 mevqlglgrv yprppsktyr gafqnlfqsv reviqnpgpr hpeaasaapp gasllllqqq

61 qqqqqqqqqq qqqqqqqqqq etsprqqqqq qgedgspqah rrgptgylvl deeqqpsqpq

121 salechperg cvpepgaava askglpqqlp appdeddsaa pstlsllgpt fpglsscsad

181 Ikdilseast mqllqqqqqe avsegsssgr areasgapts skdnylggts tisdnakelc

241 kavsvsmglg vealehlspg eqlrgdcmya pllgvppavr ptpcaplaec kgsllddsag

301 kstedtaeys pfkggytkgl egeslgcsgs aaagssgtle Ipstlslyks galdeaaayq

361 srdyynfpla lagppppppp phpharikle npldygsawa aaaaqcrygd laslhgagaa

421 gpgsgspsaa assswhtlft aeegqlygpc gggggggggg gggggggggg gggeagavap

481 ygytrppqgl agqesdftap dvwypggmvs rvpypsptcv ksemgpwmds ysgpygdmrl

541 etardhvlpi dyyfppqktc licgdeasgc hygaltcgsc kvffkraaeg kqkylcasrn

601 dctidkfrrk ncpscrlrkc yeagmtlgar klkklgnlkl qeegeasstt spteettqkl

661 tvshiegyec qpiflnvlea iepgvvcagh dnnqpdsfaa llsslnelge rqlvhvvkwa

721 kalpgfrnlh vddqmaviqy swmglmvf am gwrsftnvns rmlyfapdlv fneyrmhksr

781 mysqcvrmrh Isqefgwlqi tpqeflcmka lllfsiipvd glknqkffde Irmnyikeld

841 riiackrknp tscsrrfyql tklldsvqpi arelhqftfd llikshmvsv dfpemmaeii

901 svqvpkilsg kvkpiyfhtq

Androgen receptor, isoform 2 NP_001011645.1 (SEQ ID NO: 181)

1 milwlhslet ardhvlpidy yfppqktcli cgdeasgchy galtcgsckv ffkraaegkq

61 kylcasrndc tidkfrrknc pscrlrkcye agmtlgarkl kklgnlklqe egeassttsp

121 teettqkltv shiegyecqp iflnvleaie pgvvcaghdn nqpdsfaall sslnelgerq

181 Ivhvvkwaka Ipgfrnlhvd dqmaviqysw mglmvfamgw rsftnvnsrm lyfapdlvfn

241 eyrmhksrmy sqcvrmrhls qefgwlqitp qeflcmkall Ifsiipvdgl knqkffdelr

301 mnyikeldri iackrknpts csrrfyqltk lldsvqpiar elhqftfdll ikshmvsvdf

361 pemmaeiisv qvpkilsgkv kpiyfhtq

Androgen receptor, isoform 3 NP_001334990.1 (SEQ ID NO: 182)

1 mevqlglgrv yprppsktyr gafqnlfqsv reviqnpgpr hpeaasaapp gasllllqqq

61 qqqqqqqqqq qqqqqqqqqq etsprqqqqq qgedgspqah rrgptgylvl deeqqpsqpq

121 salechperg cvpepgaava askglpqqlp appdeddsaa pstlsllgpt fpglsscsad

181 Ikdilseast mqllqqqqqe avsegsssgr areasgapts skdnylggts tisdnakelc

241 kavsvsmglg vealehlspg eqlrgdcmya pllgvppavr ptpcaplaec kgsllddsag

301 kstedtaeys pfkggytkgl egeslgcsgs aaagssgtle Ipstlslyks galdeaaayq

361 srdyynfpla lagppppppp phpharikle npldygsawa aaaaqcrygd laslhgagaa

421 gpgsgspsaa assswhtlft aeegqlygpc gggggggggg gggggggggg gggeagavap

481 ygytrppqgl agqesdftap dvwypggmvs rvpypsptcv ksemgpwmds ysgpygdmrl

541 etardhvlpi dyyfppqktc licgdeasgc hygaltcgsc kvffkraaeg kqkylcasrn

601 dctidkfrrk ncpscrlrkc yeagmtlgek frvgnckhlk mtrp

Androgen receptor, isoform 4 NP_001334992.1 (SEQ ID NO: 183)

1 mevqlglgrv yprppsktyr gafqnlfqsv reviqnpgpr hpeaasaapp gasllllqqq

61 qqqqqqqqqq qqqqqqqqqq etsprqqqqq qgedgspqah rrgptgylvl deeqqpsqpq

121 salechperg cvpepgaava askglpqqlp appdeddsaa pstlsllgpt fpglsscsad

181 Ikdilseast mqllqqqqqe avsegsssgr areasgapts skdnylggts tisdnakelc

241 kavsvsmglg vealehlspg eqlrgdcmya pllgvppavr ptpcaplaec kgsllddsag

301 kstedtaeys pfkggytkgl egeslgcsgs aaagssgtle Ipstlslyks galdeaaayq

361 srdyynfpla lagppppppp phpharikle npldygsawa aaaaqcrygd laslhgagaa

421 gpgsgspsaa assswhtlft aeegqlygpc gggggggggg gggggggggg gggeagavap 481 ygytrppqgl agqesdftap dvwypggmvs rvpypsptcv ksemgpwmds ysgpygdmrl 541 etardhvlpi dyyfppqktc licgdeasgc hygaltcgsc kvffkraaeg kqkylcasrn 601 dctidkfrrk ncpscrlrkc yeagmtlgaa wvserilrv fgvsewlp

Androgen receptor, isoform 5 NP_001334993.1 (SEQ ID NO: 184)

1 mevqlglgrv yprppsktyr gafqnlfqsv reviqnpgpr hpeaasaapp gasllllqqq

61 qqqqqqqqqq qqqqqqqqqq etsprqqqqq qgedgspqah rrgptgylvl deeqqpsqpq

121 salechperg cvpepgaava askglpqqlp appdeddsaa pstlsllgpt fpglsscsad

181 Ikdilseast mqllqqqqqe avsegsssgr areasgapts skdnylggts tisdnakelc

241 kavsvsmglg vealehlspg eqlrgdcmya pllgvppavr ptpcaplaec kgsllddsag

301 kstedtaeys pfkggytkgl egeslgcsgs aaagssgtle Ipstlslyks galdeaaayq

361 srdyynfpla lagppppppp phpharikle npldygsawa aaaaqcrygd laslhgagaa

421 gpgsgspsaa assswhtlft aeegqlygpc gggggggggg gggggggggg gggeagavap

481 ygytrppqgl agqesdftap dvwypggmvs rvpypsptcv ksemgpwmds ysgpygdmrn

541 trrkrlwkli irsinscics pretevpvrq qk

ATPase H+ transporting accessory protein 1 NP_001174 . 2 ( SEQ ID NO : 185 )

1 mmaamatarv rmgprcaqal wrmpwlpvfl slaaaaaaaa aeqqvplvlw ssdrdlwapa

61 adtheghits dlqlstyldp alelgprnvl Iflqdklsie dftayggvfg nkqdsafsnl

121 enaldlapss Ivlpavdwya vstlttylqe klgasplhvd latlrelkln aslpalllir

181 Ipytassglm aprevltgnd evigqvlstl ksedvpytaa Itavrpsrva rdvawaggl

241 grqllqkqpv spvihppvsy ndtaprilfw aqnfsvaykd qwedltpltf gvqelnltgs

301 fwndsfarls Ityerlfgtt vtfkfilanr lypvsarhwf tmerlevhsn gsvayfnasq

361 vtgpsiys fh ceyvsslskk gsllvartqp spwqmmlqdf qiqafnvmge qfsyasdcas

421 ffspgiwmgl Itslfmlfif tyglhmilsl ktmdrfddhk gptisltqiv

B melanoma antigen 1 precursor NP_001178.1 (SEQ ID NO: 186)

1 maaravflal saqllqarlm keespvvswr lepedgtalc fif BCR/ABL fusion protein el4ab NG_050673. 1 ( SEQ ID NO : 187 )

1 gcacctgcag ggagggcagg cagctagcct gaaggctgat ccccccttcc tgttagcact

61 tttgatggga ctagtggact ttggttcaga aggaagagct atgcttgtta gggcctcttg

121 tctcctccca ggagtggaca aggtgggtta ggagcagttt ctccctgagt ggctgctgct

181 gggtggttga ggagatgcac ggcttctgtt cctagtcaca aggctgcagc agacgctcct

241 cagatgctct gtgccttgga tctggcccca ctcccgtcct cccagccctc ctctcctcca

301 gctacctgcc agccggcact tttggtcaag ctgttttgca ttcactgttg cacatatgct

361 cagtcacaca cacagcatac gctatgcaca tgtgtccaca cacaccccac ccacatccca

421 catcaccccg accccctctg ctgtccttgg aaccttatta cacttcgagt cactggtttg

481 cctgtattgt gaaaccagct ggatcctgag atccccaaga cagaaatcat gatgagtatg

541 tttttggccc atgacactgg cttaccttgt gccaggcaga tggcagccac acagtgtcca

601 ccggatggtt gattttgaag cagagttagc ttgtcacctg cctccctttc ccgggacaac

661 agaagctgac ctctttgatc tcttgcgcag atgatgagtc tccggggctc tatgggtttc

721 tgaatgtcat cgtccactca gccactggat ttaagcagag ttcaagtaag tactggtttg

781 gggaggaggg ttgcagcggc cgagccaggg tctccaccca ggaaggactc atcgggcagg

841 gtgtggggaa acagggaggt tgttcagatg accacgggac acctttgacc ctggccgctg

901 tggagtgttt gtgctggttg atgccttctg ggtgtggaat tgtttttccc ggagtggcct

961 ctgccctctc ccctagcctg tctcagatcc tgggagctgg tgagctgccc cctgcaggtg

1021 gatcgagtaa ttgcaggggt ttggcaagga ctttgacaga catccccagg ggtgcccggg

1081 agtgtggggt ccaagccagg agggctgtca gcagtgcacc ttcaccccac agcagagcag

1141 atttggctgc tctgtcgagc tggatggata ctactttttt tttcctttcc ctctaagtgg

1201 gggtctcccc cagctactgg agctgtcaga acagtgaagg ctggtaacac atgagttgca

1261 ctgtgtaagt ttctcgaggc cgggcgcagt ggctcatgcc tgtaatccca gcactttggg

1321 aggctgaggc aggtggatcg cttgagctca ggagttggag accagcctga ccaacatggt

1381 gaaaccctgt gtctactaaa aatacaaaga ttagccgggc taggcagtgg gcacctgtaa

1441 tcacaactgc ttgggaggct gagggaagag aatcgcttga acccaggagg cggaggttgc

1501 agtgagccga gcttgtgcca ctgcattcca gcctgggcga cagagcaaga ctccgcctca

1561 aaaaaaaaaa aaaaaagttc ctagaaacag caaaatgtgg agacagaaag cttaccaggg

1621 attgttgggg aatggggttg ggagagagga ctaactgcag atgaacccaa gggggacttt

1681 ttaggtgaga gcagtgtcgt gaaaagactg tggtgctgtt tgcgctcaca tttacatttc

1741 ctaaaattct ttaaacccta cacttggaat ggatgaatta catgacatgc agattgcacc

1801 ttcataacat aatctttctc ctgggcccct gtctctggct gcctcataaa cgctggtgtt

1861 tccctcgtgg gcctccctgc atccctgcat ctcctcccgg gtcctgtctg tgagcaatac

1921 agcgtgacac cctacgctgc cccgtggtcc cgggcttgtc tctccttgcc tccctgttac

1981 ctttctttct atctcttcct tgccccgtgc actcaacctt gcatccccaa accaaaccta

2041 ttattcatgg accccaaact tgttcctctt atgtcctgtc cctttgaggg gcaccaccat 2101 ccacccgcat ggccaagcca gaaaccgtgg tctgctctcc ctccgttaaa tgccattctc

2161 catcagtgag gcttcttagt catctctggc tgcctggcca ggccctggct gtggcctcct

2221 ccctggtctt tgtagctctg gatatccctg cagaaagggt ccccactacc aggcctctcc

2281 atccccagtc tcaggtagtt tttctaaaat gcaaacccca ccctgcaact taccgcccac

2341 agcccagccc actcttctcc aggcctcgcc tccctccctt ccccctgcac cccacgactt

2401 ctccagcact gagctgcttc ctgtgcccca cagtggcctg gagtcccctt tgccttaact

2461 ctttgcccca tagtacagcg gggtctgctc tgattgtagg ggcttcccac atcccccagg

2521 atggctgccc tctgctgtgg catcactgtg taacaatggc gtgtacacct ctctgtcccc

2581 accagtgcag ggcccttctc atcgtagggg ctttagctgg ggtttgtgga tcgactgagt

2641 gaacgaatgt tgtgggaagt cccgtttccc agccgcaccc agggaaattc cacagagcgg

2701 gcaggggcat cgcatgaggt gctggtgttc acgccagacc acaattaggt gtttaatttt

2761 taaaaagaaa gttacaacct ttttttttta tttttatttt ttctgattct gcaaataaca

2821 cctgctctta cagaccatgt gggtgatgtg gaaaagacct gtgaccttct ccatgtccac

2881 ttctccccac agatctgtac tgcaccctgg aggtggattc ctttgggtat tttgtgaata

2941 aagcaaagac gcgcgtctac agggacacag ctgagcca

Serine/threonine-protein kinase B-raf, isoform 1 NP_004324.2 (SEQ ID NO: 188)

1 maalsggggg gaepgqalfn gdmepeagag agaaassaad paipeevwni kqmikltqeh

61 iealldkfgg ehnppsiyle ayeeytskld alqqreqqll eslgngtdfs vsssasmdtv

121 tsssssslsv Ipsslsvfqn ptdvarsnpk spqkpivrvf Ipnkqrtvvp arcgvtvrds

181 Ikkalmmrgl ipeccavyri qdgekkpigw dtdiswltge elhvevlenv pltthnfvrk

241 tfftlafcdf crkllfqgfr cqtcgykfhq rcstevplmc vnydqldllf vskffehhpi

301 pqeeaslaet altsgsspsa pasdsigpqi Itspspsksi pipqpfrpad edhrnqfgqr

361 drsssapnvh intiepvnid dlirdqgfrg dggsttglsa tppaslpgsl tnvkalqksp

421 gpqrerksss ssedrnrmkt Igrrdssddw eipdgqitvg qrigsgsfgt vykgkwhgdv

481 avkmlnvtap tpqqlqafkn evgvlrktrh vnillfmgys tkpqlaivtq wcegsslyhh

541 Ihiietkfem iklidiarqt aqgmdylhak siihrdlksn niflhedltv kigdfglatv

601 ksrwsgshqf eqlsgsilwm apevirmqdk npysfqsdvy afgivlyelm tgqlpysnin

661 nrdqiifmvg rgylspdlsk vrsncpkamk rlmaeclkkk rderplfpqi lasiellars

721 Ipkihrsase pslnragfqt edfslyacas pktpiqaggy gafpvh

Serine/threonine-protein kinase B-raf, isoform 2 NP_001341538.1 (SEQ ID NO: 189)

1 maalsggggg gaepgqalfn gdmepeagag agaaassaad paipeevwni kqmikltqeh

61 iealldkfgg ehnppsiyle ayeeytskld alqqreqqll eslgngtdfs vsssasmdtv

121 tsssssslsv Ipsslsvfqn ptdvarsnpk spqkpivrvf Ipnkqrtvvp arcgvtvrds

181 Ikkalmmrgl ipeccavyri qdgekkpigw dtdiswltge elhvevlenv pltthnfvrk

241 tfftlafcdf crkllfqgfr cqtcgykfhq rcstevplmc vnydqldllf vskffehhpi

301 pqeeaslaet altsgsspsa pasdsigpqi Itspspsksi pipqpfrpad edhrnqfgqr

361 drsssapnvh intiepvnid dlirdqgfrg dggsttglsa tppaslpgsl tnvkalqksp

421 gpqrerksss ssedrnrmkt Igrrdssddw eipdgqitvg qrigsgsfgt vykgkwhgdv

481 avkmlnvtap tpqqlqafkn evgvlrktrh vnillfmgys tkpqlaivtq wcegsslyhh

541 Ihiietkfem iklidiarqt aqgmdylhak siihrdlksn niflhedltv kigdfglatv

601 ksrwsgshqf eqlsgsilwm apevirmqdk npysfqsdvy afgivlyelm tgqlpysnin

661 nrdqiifmvg rgylspdlsk vrsncpkamk rlmaeclkkk rderplfpqi lasiellars

721 Ipkihrsase pslnragfqt edfslyacas pktpiqaggy gefaafk

Carbonic anhydrase 9 precursor NP_001207.2 (SEQ ID NO: 190)

1 maplcpspwl pllipapapg Itvqlllsll llvpvhpqrl prmqedsplg ggssgeddpl

61 geedipseed spreedppge edlpgeedlp geedlpevkp kseeegslkl edlptveapg

121 dpqepqnnah rdkegddqsh wryggdppwp rvspacagrf qspvdirpql aafcpalrpl

181 ellgfqlppl pelrlrnngh svqltlppgl emalgpgrey ralqlhlhwg aagrpgseht

241 veghrfpaei hvvhlstafa rvdealgrpg glavlaafle egpeensaye qllsrleeia

301 eegsetqvpg Idisallpsd fsryfqyegs Ittppcaqgv iwtvfnqtvm Isakqlhtls

361 dtlwgpgdsr Iqlnfratqp Ingrvieasf pagvdsspra aepvqlnscl aagdilalvf

421 gllfavtsva flvqmrrqhr rgtkggvsyr paevaetga

G/mitotic-specific cyclin-Bl, isoform 1 NP_114172.1 (SEQ ID NO: 191)

1 malrvtrnsk inaenkakin magakrvpta paatskpglr prtalgdign kvseqlqakm

61 pmkkeakpsa tgkvidkklp kplekvpmlv pvpvsepvpe pepepepepv keeklspepi

121 Ivdtaspspm etsgcapaee dlcqafsdvi lavndvdaed gadpnlcsey vkdiyaylrq

181 leeeqavrpk yllgrevtgn mrailidwlv qvqmkfrllq etmymtvsii drfmqnncvp

241 kkmlqlvgvt amfiaskyee myppeigdfa fvtdntytkh qirqmemkil ralnfglgrp

301 Iplhflrras kigevdveqh tlakylmelt mldydmvhfp psqiaagafc lalkildnge

361 wtptlqhyls yteesllpvm qhlaknvvmv nqgltkhmtv knkyatskha kistlpqlns

421 alvqdlakav akv G/mitotic-specific cyclin-Bl, isoform 2 NP_001341773.1 (SEQ ID NO: 192)

1 malrvtrnsk inaenkakin magakrvpta paatskpglr prtalgdign kvseqlqakm

61 pmkkeakpsa tgkvidkklp kplekvpmlv pvpvsepvpe pepepepepv keeklspepi

121 Ivdtaspspm etsgcapaee dlcqafsdvi lavndvdaed gadpnlcsey vkdiyaylrq

181 leeeqavrpk yllgrevtgn mrailidwlv qvqmkfrllq etmymtvsii drfmqnncvp

241 kkmlqlvgvt amfiaskyee myppeigdfa fvtdntytkh qirqmemkil ralnfglgrp

301 Iplhflrras kigevdveqh tlakylmelt mldydmvhfp psqiaagafc lalkildnge

361 wtvknkyats khakistlpq Insalvqdla kavakv

G/mitotic-specific cyclin-Bl, isoform 3 NP_001341774.1 (SEQ ID NO: 193)

1 malrvtrnsk inaenkakin magakrvpta paatskpglr prtalgdign kvseqlqakm

61 pmkkeakpsa tgkvidkklp kplekvpmlv pvpvsepvpe pepepepepv keeklspepi

121 Ivdtaspspm etsgcapaee dlcqafsdvi lavndvdaed gadpnlcsey vkdiyaylrq

181 lenncvpkkm Iqlvgvtamf iaskyeemyp peigdfafvt dntytkhqir qmemkilral

241 nfglgrplpl hflrraskig evdveqhtla kylmeltmld ydmvhfppsq iaagafclal

301 kildngewtp tlqhylsyte esllpvmqhl aknvvmvnqg Itkhmtvknk yatskhakis

361 tlpqlnsalv qdlakavakv

CD276, isoform a precursor NP_001019907.1 (SEQ ID NO: 194)

1 mlrrrgspgm gvhvgaalga Iwfcltgale vqvpedpvva Ivgtdatlcc sfspepgfsl

61 aqlnliwqlt dtkqlvhsfa egqdqgsaya nrtalfpdll aqgnaslrlq rvrvadegsf

121 tcfvsirdfg saavslqvaa pyskpsmtle pnkdlrpgdt vtitcssyqg ypeaevfwqd

181 gqgvpltgnv ttsqmaneqg Ifdvhsilrv vlgangtysc Ivrnpvlqqd ahssvtitpq

241 rsptgavevq vpedpvvalv gtdatlrcsf spepgfslaq Inliwqltdt kqlvhsfteg

301 rdqgsayanr talfpdllaq gnaslrlqrv rvadegsftc fvsirdfgsa avslqvaapy

361 skpsmtlepn kdlrpgdtvt itcssyrgyp eaevfwqdgq gvpltgnvtt sqmaneqglf

421 dvhsvlrvvl gangtysclv rnpvlqqdah gsvtitgqpm tfppealwvt vglsvclial

481 Ivalafvcwr kikqsceeen agaedqdgeg egsktalqpl khsdskeddg qeia

CD276, isoform b precursor NP-001316557.1, NP_079516.1 (SEQ ID NO: 195)

1 mlrrrgspgm gvhvgaalga Iwfcltgale vqvpedpvva Ivgtdatlcc sfspepgfsl

61 aqlnliwqlt dtkqlvhsfa egqdqgsaya nrtalfpdll aqgnaslrlq rvrvadegsf

121 tcfvsirdfg saavslqvaa pyskpsmtle pnkdlrpgdt vtitcssyrg ypeaevfwqd

181 gqgvpltgnv ttsqmaneqg Ifdvhsvlrv vlgangtysc Ivrnpvlqqd ahgsvtitgq

241 pmtfppealw vtvglsvcli allvalafvc wrkikqscee enagaedqdg egegsktalq

301 plkhsdsked dgqeia

CD276, isoform C NP_001316558.1 (SEQ ID NO: 196)

1 mtlepnkdlr pgdtvtitcs syqgypeaev fwqdgqgvpl tgnvttsqma neqglfdvhs

61 ilrvvlgang tysclvrnpv Iqqdahssvt itpqrsptga vevqvpedpv valvgtdatl

121 rcsfspepgf slaqlnliwq ltdtkqlvhs ftegrdqgsa yanrtalfpd llaqgnaslr

181 Iqrvrvadeg sftcfvsird fgsaavslqv aapyskpsmt lepnkdlrpg dtvtitcssy

241 rgypeaevfw qdgqgvpltg nvttsqmane qglfdvhsvl rvvlgangty sclvrnpvlq

301 qdahgsvtit gqpmtfppea Iwvtvglsvc liallvalaf vcwrkikqsc eeenagaedq

361 dgegegskta Iqplkhsdsk eddgqeia

Carcinoembryonic antigen-related cell adhesion molecule 3, isoform 1 precursor NP_001806.2 (SEQ ID NO: 197)

1 mgppsasphr ecipwqglll tasllnfwnp pttaklties mplsvaegke vlllvhnlpq

61 hlfgyswykg ervdgnsliv gyvigtqqat pgaaysgret iytnaslliq nvtqndigfy

121 tlqviksdlv neeatgqfhv yqenapglpv gavagivtgv Ivgvalvaal vcflllaktg

181 rtsiqrdlke qqpqalapgr gpshssafsm splstaqapl pnprtaasiy eellkhdtni

241 ycrmdhkaev as Carcinoembryonic antigen-related cell adhesion molecule 3, isoform 2 precursor NP_001264092.1 (SEQ ID NO: 198)

1 mgppsasphr ecipwqglll tasllnfwnp pttaklties mplsvaegke vlllvhnlpq

61 hlfgyswykg ervdgnsliv gyvigtqqat pgaaysgret iytnaslliq nvtqndigfy

121 tlqviksdlv neeatgqfhv yqenapglpv gavagivtgv Ivgvalvaal vcflllaktg

181 rpwslpqlcl Idvpslhcpg pptqpqdssf hl

Carcinoembryonic antigen-related cell adhesion molecule 5, isoform 1 preprotein NP_001278413.1 , NP_004354.3 (SEQ ID NO: 199)

1 mespsapphr wcipwqrlll taslltfwnp pttaklties tpfnvaegke vlllvhnlpq

61 hlfgyswykg ervdgnrqii gyvigtqqat pgpaysgrei iypnaslliq niiqndtgfy

121 tlhviksdlv neeatgqfrv ypelpkpsis snnskpvedk davaftcepe tqdatylwwv

181 nnqslpvspr Iqlsngnrtl tlfnvtrndt asykcetqnp vsarrsdsvi Invlygpdap

241 tisplntsyr sgenlnlsch aasnppaqys wfvngtfqqs tqelfipnit vnnsgsytcq 301 ahnsdtglnr ttvttitvya eppkpfitsn nsnpvededa valtcepeiq nttylwwvnn

361 qslpvsprlq Isndnrtltl Isvtrndvgp yecgiqnels vdhsdpviln vlygpddpti

421 spsytyyrpg vnlslschaa snppaqyswl idgniqqhtq elfisnitek nsglytcqan

481 nsasghsrtt vktitvsael pkpsissnns kpvedkdava ftcepeaqnt tylwwvngqs

541 Ipvsprlqls ngnrtltlfn vtrndarayv cgiqnsvsan rsdpvtldvl ygpdtpiisp

601 pdssylsgan Inlschsasn pspqyswrin gipqqhtqvl fiakitpnnn gtyacfvsnl

661 atgrnnsivk sitvsasgts pglsagatvg imigvlvgva li

Carcinoembryonic antigen-related cell adhesion molecule 5, isoform 2 preprotein NP_001295327.1 (SEQ ID NO: 200)

1 mespsapphr wcipwqrlll taslltfwnp pttaklties tpfnvaegke vlllvhnlpq

61 hlfgyswykg ervdgnrqii gyvigtqqat pgpaysgrei iypnaslliq niiqndtgfy

121 tlhviksdlv neeatgqfrv ypelpkpsis snnskpvedk davaftcepe tqdatylwwv

181 nnqslpvspr Iqlsngnrtl tlfnvtrndt asykcetqnp vsarrsdsvi Invlygpdap

241 tisplntsyr sgenlnlsch aasnppaqys wfvngtfqqs tqelfipnit vnnsgsytcq

301 ahnsdtglnr ttvttitvye ppkpfitsnn snpvededav altcepeiqn ttylwwvnnq

361 slpvsprlql sndnrtltll svtrndvgpy ecgiqnelsv dhsdpvilnv lygpddptis

421 psytyyrpgv nlslschaas nppaqyswli dgniqqhtqe Ifisnitekn sglytcqann

481 sasghsrttv ktitvsaelp kpsissnnsk pvedkdavaf tcepeaqntt ylwwvngqsl

541 pvsprlqlsn gnrtltlfnv trndarayvc giqnsvsanr sdpvtldvly gpdtpiispp

601 dssylsganl nlschsasnp spqyswring ipqqhtqvlf iakitpnnng tyacfvsnla

661 tgrnnsivks itvsasgtsp glsagatvgi migvlvgval i

Baculoviral IAP repeat containing 2, isoform 1 NP_001157.1, NP_001243092.1 (SEQ ID NO: 201)

1 mhktasqrlf pgpsyqniks imedstilsd wtnsnkqkmk ydfscelyrm stystfpagv

61 pvserslara gfyytgvndk vkcfccglml dnwklgdspi qkhkqlypsc sfiqnlvsas

121 Igstskntsp mrnsfahsls ptlehsslfs gsysslspnp Insravedis ssrtnpysya

181 msteearflt yhmwpltfls pselaragfy yigpgdrvac facggklsnw epkddamseh

241 rrhfpncpfl ensletlrfs isnlsmqtha armrtfmywp ssvpvqpeql asagfyyvgr

301 nddvkcfccd gglrcwesgd dpwvehakwf prceflirmk gqefvdeiqg ryphlleqll

361 stsdttgeen adppiihfgp gesssedavm mntpvvksal emgfnrdlvk qtvqskiltt

421 genyktvndi vsallnaede kreeekekqa eemasddlsl irknrmalfq qltcvlpild

481 nllkanvink qehdiikqkt qiplqareli dtilvkgnaa anifknclke idstlyknlf

541 vdknmkyipt edvsglslee qlrrlqeert ckvcmdkevs vvfipcghlv vcqecapslr

601 kcpicrgiik gtvrtfls Baculoviral IAP repeat containing 2, isoform 2 NP_001243095.1 (SEQ ID NO:

202)

1 mstystfpag vpvserslar agfyytgvnd kvkcfccglm Idnwklgdsp iqkhkqlyps

61 csfiqnlvsa slgstsknts pmrnsfahsl sptlehsslf sgsysslspn plnsravedi

121 sssrtnpysy amsteearfl tyhmwpltfl spselaragf yyigpgdrva cfacggklsn

181 wepkddamse hrrhfpncpf lensletlrf sisnlsmqth aarmrtfmyw pssvpvqpeq

241 lasagfyyvg rnddvkcfcc dgglrcwesg ddpwvehakw fprceflirm kgqefvdeiq

301 gryphlleql Istsdttgee nadppiihfg pgesssedav mmntpvvksa lemgfnrdlv

361 kqtvqskilt tgenyktvnd ivsallnaed ekreeekekq aeemasddls lirknrmalf

421 qqltcvlpil dnllkanvin kqehdiikqk tqiplqarel idtilvkgna aanifknclk

481 eidstlyknl fvdknmkyip tedvsglsle eqlrrlqeer tckvcmdkev svvfipcghl

541 vvcqecapsl rkcpicrgii kgtvrtfls

Chondrosarcoma-associated gene 2/3 protein, isoform XI XP_006724920.1 (SEQ ID NO:

203)

1 mwmgliqlve gvkrkdqgfl ekefyhktni kmrceflacw paftvlgeaw rdqvdwsrll 61 rdtglvkmsr kprassplsn nhpptpkrrg sgrhplnpgp ealskfprqp grekgpikev 121 pgtkgsp

Chondrosarcoma-associated gene 2/3 protein, isoform X2 XP_016885512.1 (SEQ ID NO:

204)

1 mwmgliqlve gvkrkdqgfl ekefyhktni kmrceflacw paftvlgeaw rdqvdwsrll 61 rdtglvkmsr kprassplsn nhpptpkrfp rqpgrekgpi kevpgtkgsp Chondroitin sulfate proteoglycan 4 precursor NP_001888.2 (SEQ ID NO: 205)

1 mqsgprpplp apglalaltl tmlarlasaa sffgenhlev pvataltdid Iqlqfstsqp

61 eallllaagp adhlllqlys grlqvrlvlg qeelrlqtpa etllsdsiph tvvltvvegw

121 atlsvdgfln assavpgapl evpyglfvgg tgtlglpylr gtsrplrgcl haatlngrsl

181 Irpltpdvhe gcaeefsasd dvalgfsgph slaafpawgt qdegtleftl ttqsrqapla

241 fqaggrrgdf iyvdifeghl ravvekgqgt vllhnsvpva dgqphevsvh inahrleisv 301 dqypthtsnr gvlsyleprg slllggldae asrhlqehrl gltpeatnas llgcmedlsv

361 ngqrrglrea lltrnmaagc rleeeeyedd ayghyeafst lapeawpame Ipepcvpepg

421 Ippvfanftq lltisplvva eggtawlewr hvqptldlme aelrksqvlf svtrgarhge

481 leldipgaqa rkmftlldvv nrkarfihdg sedtsdqlvl evsvtarvpm psclrrgqty

541 llpiqvnpvn dpphiifphg slmvilehtq kplgpevfqa ydpdsacegl tfqvlgtssg

601 Ipverrdqpg epatefscre leagslvyvh rggpaqdltf rvsdglqasp patlkvvair

661 paiqihrstg Irlaqgsamp ilpanlsvet navgqdvsvl frvtgalqfg elqkqgaggv

721 egaewwatqa fhqrdveqgr vrylstdpqh haydtvenla levqvgqeil snlsfpvtiq

781 ratvwmlrle plhtqntqqe tlttahleat leeagpsppt fhyevvqapr kgnlqlqgtr

841 Isdgqgftqd diqagrvtyg ataraseave dtfrfrvtap pyfsplytfp ihiggdpdap

901 vltnvllvvp eggegvlsad hlfvkslnsa sylyevmerp rhgrlawrgt qdkttmvtsf

961 tnedllrgrl vyqhddsett eddipfvatr qgessgdmaw eevrgvfrva iqpvndhapv

1021 qtisrifhva rggrrllttd dvafsdadsg fadaqlvltr kdllfgsiva vdeptrpiyr

1081 ftqedlrkrr vlfvhsgadr gwiqlqvsdg qhqatallev qasepylrva ngsslvvpqg

1141 gqgtidtavl hldtnldirs gdevhyhvta gprwgqlvra gqpatafsqq dlldgavlys

1201 hngslsprdt mafsveagpv htdatlqvti alegplaplk Ivrhkkiyvf qgeaaeirrd

1261 qleaaqeavp padivfsvks ppsagylvmv srgaladepp sldpvqsfsq eavdtgrvly

1321 Ihsrpeawsd afsldvasgl gaplegvlve levlpaaipl eaqnfsvpeg gsltlappll

1381 rvsgpyfptl Iglslqvlep pqhgalqked gpqartlsaf swrmveeqli ryvhdgsetl

1441 tdsfvlmana semdrqshpv aftvtvlpvn dqppilttnt glqmwegata pipaealrst

1501 dgdsgsedlv ytieqpsngr vvlrgapgte vrsftqaqld gglvlfshrg tldggfrfrl

1561 sdgehtspgh ffrvtaqkqv llslkgsqtl tvcpgsvqpl ssqtlrasss agtdpqllly

1621 rvvrgpqlgr Ifhaqqdstg ealvnftqae vyagnilyeh emppepfwea hdtlelqlss

1681 ppardvaatl avavsfeaac pqrpshlwkn kglwvpegqr aritvaalda snllasvpsp

1741 qrsehdvlfq vtqfpsrgql Ivseeplhag qphflqsqla agqlvyahgg ggtqqdgfhf

1801 rahlqgpaga svagpqtsea faitvrdvne rppqpqasvp Irltrgsrap israqlsvvd

1861 pdsapgeiey evqraphngf Islvggglgp vtrftqadvd sgrlafvang ssvagifqls

1921 msdgaspplp mslavdilps aievqlrapl evpqalgrss Isqqqlrvvs dreepeaayr

1981 liqgpqyghl Ivggrptsaf sqfqidqgev vfaftnfsss hdhfrvlala rgvnasavvn

2041 vtvrallhvw aggpwpqgat Irldptvlda gelanrtgsv prfrllegpr hgrvvrvpra

2101 rtepggsqlv eqftqqdled grlglevgrp egrapgpagd sltlelwaqg vppavasldf

2161 atepynaarp ysvallsvpe aarteagkpe sstptgepgp masspepava kggflsflea

2221 nmfsviipmc Ivllllalil pllfylrkrn ktgkhdvqvl takprnglag dtetfrkvep

2281 gqaipltavp gqgpppggqp dpellqfcrt pnpalkngqy wv

Cancer/testis antigen 2 isoform LAGE-la NP_758965.2 (SEQ ID NO: 206)

1 mqaegrgtgg stgdadgpgg pgipdgpggn aggpgeagat ggrgprgaga arasgprgga

61 prgphggaas aqdgrcpcga rrpdsrllel hitmpfsspm eaelvrrils rdaaplprpg

121 avlkdftvsg nllfirltaa dhrqlqlsis sclqqlsllm witqcflpvf laqapsgqrr

Cancer/testis antigen 2 isoform LAGE-lb NP_066274.2 (SEQ ID NO: 207)

1 mqaegrgtgg stgdadgpgg pgipdgpggn aggpgeagat ggrgprgaga arasgprgga

61 prgphggaas aqdgrcpcga rrpdsrllel hitmpfsspm eaelvrrils rdaaplprpg

121 avlkdftvsg nllfmsvrdq dregagrmrv vgwglgsasp egqkardlrt pkhkvseqrp

181 gtpgppppeg aqgdgcrgva fnvmfsaphi

Transcriptional repressor CTCFL, isoform 1 NP_001255969.1, NP_001255970.1, NP_542185.2 (SEQ ID NO: 208)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwin Ihrhsekcgs geaksaasgk grrtrkrkqt ilkeatkgqk

601 eaakgwkeaa ngdeaaaeea sttkgeqfpg emfpvacret tarvkeevde gvtcemllnt

661 mdk

Transcriptional repressor CTCFL, isoform 2 NP_001255971.1 (SEQ ID NO: 209)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv 61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll 121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli 181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwin Ihrhsekcgs geaksaasgk grrtrkrkqt ilkeatkgqk

601 eaakgwkeaa ngdaaaeeas ttkgeqfpge mfpvacrett arvkeevdeg vtcemllntm

661 dk

Transcriptional repressor CTCFL, isoform 3 NP_001255972.1 (SEQ ID NO: 210)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwin Ihrhsekcgs geaksaasgk grrtrkrkqt ilkeatkgqk

601 eaakgwkeaa ngdeaaaeea sttkgeqfpg emfpvacret tarvkeevde gvtcemllnt

661 mdnsagctgr mmlvsawllg rpqetynqgr rrrgsrrvtw

Transcriptional repressor CTCFL, isoform 4 NP_001255973.1 (SEQ ID NO: 211)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwin Ihrhsekcgs geaksaasgk grrtrkrkqt ilkeatkgqk

601 eaakgwkeaa ngdgvisahr nlcllgssds hasvsgagit darhhawliv llflvemgfy

661 hvshs

Transcriptional repressor CTCFL, isoform 5 NP_001255974.1 (SEQ ID NO: 212)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwil wvgnsevael ggpgsgpllr Iqsgcppglh hpkaglgped

601 plpgqlrhtt agtglssllq gplcraa

Transcriptional repressor CTCFL, isoform 6 NP_001255975.1 (SEQ ID NO: 213)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgvhmrnl haysaaelkc rycsavfher

421 yaliqhqkth knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln

481 ahfrkyhdan fiptvykcsk cgkgfsrwin Ihrhsekcgs geaksaasgk grrtrkrkqt

541 ilkeatkgqk eaakgwkeaa ngdeaaaeea sttkgeqfpg emfpvacret tarvkeevde

601 gvtcemllnt mdk

Transcriptional repressor CTCFL, isoform 7 NP_001255976.1 (SEQ ID NO: 214)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv 61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveasklkrh

361 vrshtgerpf qccqcsyasr dtyklkrhmr thsgekpyec hichtrftqs gtmkihilqk

421 hgenvpkyqc phcatiiark sdlrvhmrnl haysaaelkc rycsavfher yaliqhqkth

481 knekrfkckh csyackqerh mtahirthtg ekpftclscn kcfrqkqlln ahfrkyhdan

541 fiptvykcsk cgkgfsrwit skwsglkpqt fit

Transcriptional repressor CTCFL, isoform 8 NP_001255977.1 (SEQ ID NO: 215)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya sveerhmtah

361 irthtgekpf tclscnkcfr qkqllnahfr kyhdanfipt vykcskcgkg fsrwilwvgn

421 sevaelggpg sgpllrlqsg cppglhhpka glgpedplpg qlrhttagtg Issllqgplc

481 raa

Transcriptional repressor CTCFL, isoform 9 NP_001255978.1 (SEQ ID NO: 216)

1 msgdersdei vltvsnsnve eqedqptagq adaekakstk nqrktkgakg tfhcdvcmft

61 ssrmssfnrh mkthtsekph Ichlclktfr tvtllrnhvn thtgtrpykc ndcnmafvts

121 gelvrhrryk hthekpfkcs mckyasveas klkrhvrsht gerpfqccqc syasrdtykl

181 krhmrthsge kpyechicht rftqsgtmki hilqkhgenv pkyqcphcat iiarksdlrv

241 hmrnlhaysa aelkcrycsa vfheryaliq hqkthknekr fkckhcsyac kqerhmtahi

301 rthtgekpft clscnkcfrq kqllnahfrk yhdanfiptv ykcskcgkgf srwinlhrhs

361 ekcgsgeaks aasgkgrrtr krkqtilkea tkgqkeaakg wkeaangdgv isahrnlcll

421 gssdshasvs gagitdarhh awlivllflv emgfyhvshs

Transcriptional repressor CTCFL, isoform 10 NP_001255979.1 (SEQ ID NO: 217)

1 msgdersdei vltvsnsnve eqedqptagq adaekakstk nqrktkgakg tfhcdvcmft 61 ssrmssfnrh mkthtsekph Ichlclktfr tvtllrnhvn thtgtrpykc ndcnmafvts 121 gelvrhrryk hthekpfkcs mckyasveas klkrhvrsht gerpfqccqc syasrdtykl 181 krhmrthsge kpyechicht rftqsgtmki hilqkhgenv pkyqcphcat iiarksdlrv 241 hmrnlhaysa aelkcrycsa vfheryaliq hqkthknekr fkckhcsyac kqerhmtahi 301 rthtgekpft clscnkcfrq kqllnahfrk yhdanfiptv ykcskcgkgf srwilwvgns 361 evaelggpgs gpllrlqsgc ppglhhpkag Igpedplpgq Irhttagtgl ssllqgplcr 421 aa

Transcriptional repressor CTCFL, isoform 11 NP_001255980.1, NP_001255981.1 (SEQ ID NO: 218)

1 maateisvls eqftkikele Impekglkee ekdgvcrekd hrspseleae rtsgafqdsv

61 leeevelvla pseesekyil tlqtvhftse avelqdmsll siqqqegvqv vvqqpgpgll

121 wleegprqsl qqcvaisiqq elyspqemev Iqfhaleenv mvasedskla vslaettgli

181 kleeeqeknq llaertkeql ffvetmsgde rsdeivltvs nsnveeqedq ptagqadaek

241 akstknqrkt kgakgtfhcd vcmftssrms sfnrhmktht sekphlchlc Iktfrtvtll

301 rnhvnthtgt rpykcndcnm afvtsgelvr hrrykhthek pfkcsmckya svevkpfldl

361 klhgilveaa vqvtpsvtns ricykqafyy sykiyagnnm hsll

Transcriptional repressor CTCFL, isoform 12 NP_001255983.1 (SEQ ID NO: 219) 1 mftssrmssf nrhmkthtse kphlchlclk tfrtvtllrn hvnthtgtrp ykcndcnmaf

61 vtsgelvrhr rykhthekpf kcsmckyasv easklkrhvr shtgerpfqc cqcsyasrdt

121 yklkrhmrth sgekpyechi chtrftqsgt mkihilqkhg envpkyqcph catiiarksd

181 Irvhmrnlha ysaaelkcry csavfherya liqhqkthkn ekrfkckhcs yackqerhmt

241 ahirthtgek pftclscnkc frqkqllnah frkyhdanfi ptvykcskcg kgfsrwinlh

301 rhsekcgsge aksaasgkgr rtrkrkqtil keatkgqkea akgwkeaang dgvisahrnl

361 cllgssdsha svsgagitda rhhawlivll flvemgfyhv shs

Transcriptional repressor CTCFL, isoform 13 NP_001255984.1 (SEQ ID NO: 220)

1 mftssrmssf nrhmkthtse kphlchlclk tfrtvtllrn hvnthtgtrp ykcndcnmaf

61 vtsgelvrhr rykhthekpf kcsmckyasv easklkrhvr shtgerpfqc cqcsyasrdt

121 yklkrhmrth sgekpyechi chtrftqsgt mkihilqkhg envpkyqcph catiiarksd

181 Irvhmrnlha ysaaelkcry csavfherya liqhqkthkn ekrfkckhcs yackqerhmt

241 ahirthtgek pftclscnkc frqkqllnah frkyhdanfi ptvykcskcg kgfsrwvly

Cytochrome P450 1B1 NP_000095.2 (SEQ ID NO: 221) 1 mgtslspndp wplnplsiqq ttlllllsvl atvhvgqrll rqrrrqlrsa ppgpfawpli

61 gnaaavgqaa hlsfarlarr ygdvfqirlg scpivvlnge raihqalvqq gsafadrpaf

121 asfrvvsggr smafghyseh wkvqrraahs mmrnfftrqp rsrqvleghv Isearelval

181 Ivrgsadgaf Idprpltvva vanvmsavcf gcryshddpe frellshnee fgrtvgagsl

241 vdvmpwlqyf pnpvrtvfre feqlnrnfsn fildkflrhc eslrpgaapr dmmdafilsa

301 ekkaagdshg ggarldlenv patitdifga sqdtlstalq wllllftryp dvqtrvqael

361 dqvvgrdrlp cmgdqpnlpy vlaflyeamr fssfvpvtip hattantsvl gyhipkdtvv

421 fvnqwsvnhd plkwpnpenf dparfldkdg linkdltsrv mifsvgkrrc igeelskmql

481 flfisilahq cdfranpnep akmnfsyglt ikpksfkvnv tlresmelld savqnlqake

541 tcq Epidermal growth factor receptor, isoform a precursor NP_005219.2 (SEQ ID NO: 222)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf

181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc

241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv

301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk

361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf

421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl

481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn

541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm

601 genntlvwky adaghvchlc hpnctygctg pglegcptng pkipsiatgm vgalllllvv

661 algiglfmrr rhivrkrtlr rllqerelve pltpsgeapn qallrilket efkkikvlgs

721 gafgtvykgl wipegekvki pvaikelrea tspkankeil deayvmasvd nphvcrllgi

781 cltstvqlit qlmpfgclld yvrehkdnig sqyllnwcvq iakgmnyled rrlvhrdlaa

841 rnvlvktpqh vkitdfglak llgaeekeyh aeggkvpikw malesilhri ythqsdvwsy

901 gvtvwelmtf gskpydgipa seissilekg erlpqppict idvymimvkc wmidadsrpk

961 freliiefsk mardpqrylv iqgdermhlp sptdsnfyra Imdeedmddv vdadeylipq

1021 qgffsspsts rtpllsslsa tsnnstvaci drnglqscpi kedsflqrys sdptgalted

1081 siddtflpvp eyinqsvpkr pagsvqnpvy hnqplnpaps rdphyqdphs tavgnpeyln

1141 tvqptcvnst fdspahwaqk gshqisldnp dyqqdffpke akpngifkgs taenaeylrv

1201 apqssefiga Epidermal growth factor receptor, isoform b precursor NP_958439.1 (SEQ ID NO: 223)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf

181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc

241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv

301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk

361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf

421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl

481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn

541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm

601 genntlvwky adaghvchlc hpnctygs

Epidermal growth factor receptor, isoform c precursor NP_958440.1 (SEQ ID NO: 224)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf

181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc

241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv

301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk

361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgls

Epidermal growth factor receptor, isoform d precursor NP_958441.1 (SEQ ID NO: 225)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf

181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc

241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv

301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk 361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf

421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl

481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn

541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm

601 genntlvwky adaghvchlc hpnctygpgn eslkamlfcl fklsscnqsn dgsvshqsgs

661 paaqesclgw ipsllpsefq Igwggcshlh awpsasviit assch

Epidermal growth factor receptor, isoform e precursor NP_001333826.1 (SEQ ID NO:

226)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qgqkcdpscp ngscwgagee ncqkltkiic aqqcsgrcrg

181 kspsdcchnq caagctgpre sdclvcrkfr deatckdtcp plmlynptty qmdvnpegky

241 sfgatcvkkc prnyvvtdhg scvracgads yemeedgvrk ckkcegpcrk vcngigigef

301 kdslsinatn ikhfknctsi sgdlhilpva frgdsfthtp pldpqeldil ktvkeitgfl

361 liqawpenrt dlhafenlei irgrtkqhgq fslavvslni tslglrslke isdgdviisg

421 nknlcyanti nwkklfgtsg qktkiisnrg ensckatgqv chalcspegc wgpeprdcvs

481 crnvsrgrec vdkcnllege prefvensec iqchpeclpq amnitctgrg pdnciqcahy

541 idgphcvktc pagvmgennt Ivwkyadagh vchlchpnct ygctgpgleg cptngpkips

601 iatgmvgall lllvvalgig Ifmrrrhivr krtlrrllqe relvepltps geapnqallr

661 ilketefkki kvlgsgafgt vykglwipeg ekvkipvaik elreatspka nkeildeayv

721 masvdnphvc rllgicltst vqlitqlmpf gclldyvreh kdnigsqyll nwcvqiakgm

781 nyledrrlvh rdlaarnvlv ktpqhvkitd fglakllgae ekeyhaeggk vpikwmales

841 ilhriythqs dvwsygvtvw elmtfgskpy dgipaseiss ilekgerlpq ppictidvym

901 imvkcwmida dsrpkfreli iefskmardp qrylviqgde rmhlpsptds nfyralmdee

961 dmddvvdade ylipqqgffs spstsrtpll sslsatsnns tvacidrngl qscpikedsf

1021 Iqryssdptg altedsiddt flpvpgewlv wkqscsstss thsaaaslqc psqvlppasp

1081 egetvadlqt q

Epidermal growth factor receptor, isoform f precursor NP_001333827.1 (SEQ ID NO:

227)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf

181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc

241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv

301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk

361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf

421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl

481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn

541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm

601 genntlvwky adaghvchlc hpnctygctg pglegcptng pkipsiatgm vgalllllvv

661 algiglfmrr rhivrkrtlr rllqerelve pltpsgeapn qallrilket efkkikvlgs

721 gafgtvykgl wipegekvki pvaikelrea tspkankeil deayvmasvd nphvcrllgi

781 cltstvqlit qlmpfgclld yvrehkdnig sqyllnwcvq iakgmnyled rrlvhrdlaa

841 rnvlvktpqh vkitdfglak llgaeekeyh aeggkvpikw malesilhri ythqsdvwsy

901 gvtvwelmtf gskpydgipa seissilekg erlpqppict idvymimvkc wmidadsrpk

961 freliiefsk mardpqrylv iqgdermhlp sptdsnfyra Imdeedmddv vdadeylipq

1021 qgffsspsts rtpllsslsa tsnnstvaci drnglqscpi kedsflqrys sdptgalted

1081 siddtflpvp gewlvwkqsc sstssthsaa aslqcpsqvl ppaspegetv adlqtq

Epidermal growth factor receptor, isoform g precursor NP_001333828.1 (SEQ ID NO:

228)

1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev

61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala

121 vlsnydankt glkelpmrnl qgqkcdpscp ngscwgagee ncqkltkiic aqqcsgrcrg

181 kspsdcchnq caagctgpre sdclvcrkfr deatckdtcp plmlynptty qmdvnpegky

241 sfgatcvkkc prnyvvtdhg scvracgads yemeedgvrk ckkcegpcrk vcngigigef

301 kdslsinatn ikhfknctsi sgdlhilpva frgdsfthtp pldpqeldil ktvkeitgfl

361 liqawpenrt dlhafenlei irgrtkqhgq fslavvslni tslglrslke isdgdviisg

421 nknlcyanti nwkklfgtsg qktkiisnrg ensckatgqv chalcspegc wgpeprdcvs

481 crnvsrgrec vdkcnllege prefvensec iqchpeclpq amnitctgrg pdnciqcahy

541 idgphcvktc pagvmgennt Ivwkyadagh vchlchpnct ygctgpgleg cptngpkips

601 iatgmvgall lllvvalgig Ifmrrrhivr krtlrrllqe relvepltps geapnqallr 661 ilketefkki kvlgsgafgt vykglwipeg ekvkipvaik elreatspka nkeildeayv

721 masvdnphvc rllgicltst vqlitqlmpf gclldyvreh kdnigsqyll nwcvqiakgm

781 nyledrrlvh rdlaarnvlv ktpqhvkitd fglakllgae ekeyhaeggk vpikwmales

841 ilhriythqs dvwsygvtvw elmtfgskpy dgipaseiss ilekgerlpq ppictidvym

901 imvkcwmida dsrpkfreli iefskmardp qrylviqgde rmhlpsptds nfyralmdee

961 dmddvvdade ylipqqgffs spstsrtpll sslsatsnns tvacidrngl qscpikedsf

1021 Iqryssdptg altedsiddt flpvpeyinq svpkrpagsv qnpvyhnqpl npapsrdphy

1081 qdphstavgn peylntvqpt cvnstfdspa hwaqkgshqi sldnpdyqqd ffpkeakpng

1141 ifkgstaena eylrvapqss efiga

Epidermal growth factor receptor, isoform h NP_001333829.1 (SEQ ID NO: 229)

1 mfnncevvlg nleityvqrn ydlsflktiq evagyvlial ntveriplen Iqiirgnmyy

61 ensyalavls nydanktglk elpmrnlqei Ihgavrfsnn palcnvesiq wrdivssdfl

121 snmsmdfqnh Igscqkcdps cpngscwgag eencqkltki icaqqcsgrc rgkspsdcch

181 nqcaagctgp resdclvcrk frdeatckdt cpplmlynpt tyqmdvnpeg kysfgatcvk

241 kcprnyvvtd hgscvracga dsyemeedgv rkckkcegpc rkvcngigig efkdslsina

301 tnikhfknct sisgdlhilp vafrgdsfth tppldpqeld ilktvkeitg flliqawpen

361 rtdlhafenl eiirgrtkqh gqfslavvsl nitslglrsl keisdgdvii sgnknlcyan

421 tinwkklfgt sgqktkiisn rgensckatg qvchalcspe gcwgpeprdc vscrnvsrgr

481 ecvdkcnlle geprefvens eciqchpecl pqamnitctg rgpdnciqca hyidgphcvk

541 tcpagvmgen ntlvwkyada ghvchlchpn ctygctgpgl egcptngpki psiatgmvga

601 lllllvvalg iglfmrrrhi vrkrtlrrll qerelveplt psgeapnqal Irilketefk

661 kikvlgsgaf gtvykglwip egekvkipva ikelreatsp kankeildea yvmasvdnph

721 vcrllgiclt stvqlitqlm pfgclldyvr ehkdnigsqy llnwcvqiak gmnyledrrl

781 vhrdlaarnv Ivktpqhvki tdfglakllg aeekeyhaeg gkvpikwmal esilhriyth

841 qsdvwsygvt vwelmtfgsk pydgipasei ssilekgerl pqppictidv ymimvkcwmi

901 dadsrpkfre liiefskmar dpqrylviqg dermhlpspt dsnfyralmd eedmddvvda

961 deylipqqgf fsspstsrtp llsslsatsn nstvacidrn glqscpiked sflqryssdp

1021 tgaltedsid dtflpvpeyi nqsvpkrpag svqnpvyhnq plnpapsrdp hyqdphstav

1081 gnpeylntvq ptcvnstfds pahwaqkgsh qisldnpdyq qdffpkeakp ngifkgstae

1141 naeylrvapq ssefiga

Epidermal growth factor receptor, isoform i precursor NP_001333870.1 (SEQ ID NO: 230)

1 mrpsgtagaa llallaalcp asraleekkg nyvvtdhgsc vracgadsye meedgvrkck

61 kcegpcrkvc ngigigefkd slsinatnik hfknctsisg dlhilpvafr gdsfthtppl

121 dpqeldilkt vkeitgflli qawpenrtdl hafenleiir grtkqhgqfs lavvslnits

181 Iglrslkeis dgdviisgnk nlcyantinw kklfgtsgqk tkiisnrgen sckatgqvch

241 alcspegcwg peprdcvscr nvsrgrecvd kcnllegepr efvenseciq chpeclpqam

301 nitctgrgpd nciqcahyid gphcvktcpa gvmgenntlv wkyadaghvc hlchpnctyg

361 ctgpglegcp tngpkipsia tgmvgallll Ivvalgiglf mrrrhivrkr tlrrllqere

421 Ivepltpsge apnqallril ketefkkikv Igsgafgtvy kglwipegek vkipvaikel

481 reatspkank eildeayvma svdnphvcrl Igicltstvq litqlmpfgc lldyvrehkd

541 nigsqyllnw cvqiakgmny ledrrlvhrd laarnvlvkt pqhvkitdfg lakllgaeek

601 eyhaeggkvp ikwmalesil hriythqsdv wsygvtvwel mtfgskpydg ipaseissil

661 ekgerlpqpp ictidvymim vkcwmidads rpkfreliie fskmardpqr ylviqgderm

721 hlpsptdsnf yralmdeedm ddvvdadeyl ipqqgffssp stsrtpllss Isatsnnstv

781 acidrnglqs cpikedsflq ryssdptgal tedsiddtfl pvpeyinqsv pkrpagsvqn

841 pvyhnqplnp apsrdphyqd phstavgnpe ylntvqptcv nstfdspahw aqkgshqisl

901 dnpdyqqdff pkeakpngif kgstaenaey Irvapqssef iga

Epithelial cell adhesion molecule NP_002345.2 (SEQ ID NO: 231)

1 mappqvlafg lllaaatatf aaaqeecvce nyklavncfv nnnrqcqcts vgaqntvics

61 klaakclvmk aemngsklgr rakpegalqn ndglydpdcd esglfkakqc ngtsmcwcvn

121 tagvrrtdkd teitcservr tywiiielkh karekpydsk slrtalqkei ttryqldpkf

181 itsilyennv itidlvqnss qktqndvdia dvayyfekdv kgeslfhskk mdltvngeql

241 dldpgqtliy yvdekapefs mqglkagvia vivvvviavv agivvlvisr kkrmakyeka

301 eikemgemhr elna

Ephrin type-A receptor 2, isoform 1 precursor NP_004422.2 (SEQ ID NO: 232)

1 melqaaracf allwgcalaa aaaaqgkevv lldfaaagge Igwlthpygk gwdlmqnimn

61 dmpiymysvc nvmsgdqdnw Irtnwvyrge aerifielkf tvrdcnsfpg gasscketfn

121 lyyaesdldy gtnfqkrlft kidtiapdei tvssdfearh vklnveersv gpltrkgfyl

181 afqdigacva llsvrvyykk cpellqglah fpetiagsda pslatvagtc vdhavvppgg

241 eeprmhcavd gewlvpigqc Icqagyekve dacqacspgf fkfeasespc lecpehtlps 301 pegatscece egffrapqdp asmpctrpps aphyltavgm gakvelrwtp pqdsggredi

361 vysvtceqcw pesgecgpce asvrysepph gltrtsvtvs dlephmnytf tvearngvsg

421 Ivtsrsfrta svsinqtepp kvrlegrstt slsvswsipp pqqsrvwkye vtyrkkgdsn

481 synvrrtegf svtlddlapd ttylvqvqal tqegqgagsk vhefqtlspe gsgnlavigg

541 vavgvvlllv lagvgffihr rrknqrarqs pedvyfskse qlkplktyvd phtyedpnqa

601 vlkftteihp scvtrqkvig agefgevykg mlktssgkke vpvaiktlka gytekqrvdf

661 Igeagimgqf shhniirleg viskykpmmi iteymengal dkflrekdge fsvlqlvgml

721 rgiaagmkyl anmnyvhrdl aarnilvnsn Ivckvsdfgl srvleddpea tyttsggkip

781 irwtapeais yrkftsasdv wsfgivmwev mtygerpywe Isnhevmkai ndgfrlptpm

841 dcpsaiyqlm mqcwqqerar rpkfadivsi Idklirapds Iktladfdpr vsirlpstsg

901 segvpfrtvs ewlesikmqq ytehfmaagy taiekvvqmt nddikrigvr Ipghqkriay

961 sllglkdqvn tvgipi

Ephrin type-A receptor 2, isoform 2 NP_001316019.1 (SEQ ID NO: 233)

1 mqnimndmpi ymysvcnvms gdqdnwlrtn wvyrgeaeri fielkftvrd cnsfpggass

61 cketfnlyya esdldygtnf qkrlftkidt iapdeitvss dfearhvkln veersvgplt

121 rkgfylafqd igacvallsv rvyykkcpel Iqglahfpet iagsdapsla tvagtcvdha

181 vvppggeepr mhcavdgewl vpigqclcqa gyekvedacq acspgffkfe asespclecp

241 ehtlpspega tsceceegff rapqdpasmp ctrppsaphy Itavgmgakv elrwtppqds

301 ggredivysv tceqcwpesg ecgpceasvr ysepphgltr tsvtvsdlep hmnytftvea

361 rngvsglvts rsfrtasvsi nqteppkvrl egrsttslsv swsipppqqs rvwkyevtyr

421 kkgdsnsynv rrtegfsvtl ddlapdttyl vqvqaltqeg qgagskvhef qtlspegsgn

481 laviggvavg vvlllvlagv gffihrrrkn qrarqspedv yfskseqlkp Iktyvdphty

541 edpnqavlkf tteihpscvt rqkvigagef gevykgmlkt ssgkkevpva iktlkagyte

601 kqrvdflgea gimgqfshhn iirlegvisk ykpmmiitey mengaldkfl rekdgefsvl

661 qlvgmlrgia agmkylanmn yvhrdlaarn ilvnsnlvck vsdfglsrvl eddpeatytt

721 sggkipirwt apeaisyrkf tsasdvwsfg ivmwevmtyg erpywelsnh evmkaindgf

781 rlptpmdcps aiyqlmmqcw qqerarrpkf adivsildkl irapdslktl adfdprvsir

841 Ipstsgsegv pfrtvsewle sikmqqyteh fmaagytaie kvvqmtnddi krigvrlpgh

901 qkriaysllg Ikdqvntvgi pi

Receptor-tyrosine-protein kinase erbB-2, isoform a precursor NP_004439.2 (SEQ ID NO: 234)

1 melaalcrwg lllallppga astqvctgtd mklrlpaspe thldmlrhly qgcqvvqgnl

61 eltylptnas Isflqdiqev qgyvliahnq vrqvplqrlr ivrgtqlfed nyalavldng

121 dplnnttpvt gaspgglrel qlrslteilk ggvliqrnpq Icyqdtilwk difhknnqla

181 Itlidtnrsr achpcspmck gsrcwgesse dcqsltrtvc aggcarckgp Iptdccheqc

241 aagctgpkhs dclaclhfnh sgicelhcpa Ivtyntdtfe smpnpegryt fgascvtacp

301 ynylstdvgs ctlvcplhnq evtaedgtqr cekcskpcar vcyglgmehl revravtsan

361 iqefagckki fgslaflpes fdgdpasnta plqpeqlqvf etleeitgyl yisawpdslp

421 dlsvfqnlqv irgrilhnga ysltlqglgi swlglrslre Igsglalihh nthlcfvhtv

481 pwdqlfrnph qallhtanrp edecvgegla chqlcarghc wgpgptqcvn csqflrgqec

541 veecrvlqgl preyvnarhc Ipchpecqpq ngsvtcfgpe adqcvacahy kdppfcvarc

601 psgvkpdlsy mpiwkfpdee gacqpcpinc thscvdlddk gcpaeqrasp Itsiisavvg

661 illvvvlgvv fgilikrrqq kirkytmrrl Iqetelvepl tpsgampnqa qmrilketel

721 rkvkvlgsga fgtvykgiwi pdgenvkipv aikvlrents pkankeilde ayvmagvgsp

781 yvsrllgicl tstvqlvtql mpygclldhv renrgrlgsq dllnwcmqia kgmsyledvr

841 Ivhrdlaarn vlvkspnhvk itdfglarll dideteyhad ggkvpikwma lesilrrrft

901 hqsdvwsygv tvwelmtfga kpydgipare ipdllekger Ipqppictid vymimvkcwm

961 idsecrprfr elvsefsrma rdpqrfvviq nedlgpaspl dstfyrslle dddmgdlvda

1021 eeylvpqqgf fcpdpapgag gmvhhrhrss strsgggdlt Iglepseeea prsplapseg

1081 agsdvfdgdl gmgaakglqs Ipthdpsplq rysedptvpl psetdgyvap Itcspqpeyv

1141 nqpdvrpqpp spregplpaa rpagatlerp ktlspgkngv vkdvfafgga venpeyltpq

1201 ggaapqphpp pafspafdnl yywdqdpper gappstfkgt ptaenpeylg Idvpv

Receptor-tyrosine-protein kinase erbB-2, isoform b NP_001005862.1 (SEQ ID NO: 235)

1 mklrlpaspe thldmlrhly qgcqvvqgnl eltylptnas Isflqdiqev qgyvliahnq

61 vrqvplqrlr ivrgtqlfed nyalavldng dplnnttpvt gaspgglrel qlrslteilk

121 ggvliqrnpq Icyqdtilwk difhknnqla Itlidtnrsr achpcspmck gsrcwgesse

181 dcqsltrtvc aggcarckgp Iptdccheqc aagctgpkhs dclaclhfnh sgicelhcpa

241 Ivtyntdtfe smpnpegryt fgascvtacp ynylstdvgs ctlvcplhnq evtaedgtqr

301 cekcskpcar vcyglgmehl revravtsan iqefagckki fgslaflpes fdgdpasnta

361 plqpeqlqvf etleeitgyl yisawpdslp dlsvfqnlqv irgrilhnga ysltlqglgi 421 swlglrslre Igsglalihh nthlcfvhtv pwdqlfrnph qallhtanrp edecvgegla

481 chqlcarghc wgpgptqcvn csqflrgqec veecrvlqgl preyvnarhc Ipchpecqpq

541 ngsvtcfgpe adqcvacahy kdppfcvarc psgvkpdlsy mpiwkfpdee gacqpcpinc

601 thscvdlddk gcpaeqrasp Itsiisavvg illvvvlgvv fgilikrrqq kirkytmrrl

661 Iqetelvepl tpsgampnqa qmrilketel rkvkvlgsga fgtvykgiwi pdgenvkipv

721 aikvlrents pkankeilde ayvmagvgsp yvsrllgicl tstvqlvtql mpygclldhv

781 renrgrlgsq dllnwcmqia kgmsyledvr Ivhrdlaarn vlvkspnhvk itdfglarll

841 dideteyhad ggkvpikwma lesilrrrft hqsdvwsygv tvwelmtfga kpydgipare

901 ipdllekger Ipqppictid vymimvkcwm idsecrprfr elvsefsrma rdpqrfvviq

961 nedlgpaspl dstfyrslle dddmgdlvda eeylvpqqgf fcpdpapgag gmvhhrhrss

1021 strsgggdlt Iglepseeea prsplapseg agsdvfdgdl gmgaakglqs Ipthdpsplq

1081 rysedptvpl psetdgyvap Itcspqpeyv nqpdvrpqpp spregplpaa rpagatlerp

1141 ktlspgkngv vkdvfafgga venpeyltpq ggaapqphpp pafspafdnl yywdqdpper

1201 gappstfkgt ptaenpeylg Idvpv

Receptor-tyrosine-protein kinase erbB-2, isoform c NP_001276865.1 (SEQ ID NO: 236)

1 mprgswkpqv ctgtdmklrl paspethldm Irhlyqgcqv vqgnleltyl ptnaslsflq

61 diqevqgyvl iahnqvrqvp Iqrlrivrgt qlfednyala vldngdplnn ttpvtgaspg

121 glrelqlrsl teilkggvli qrnpqlcyqd tilwkdifhk nnqlaltlid tnrsrachpc

181 spmckgsrcw gessedcqsl trtvcaggca rckgplptdc cheqcaagct gpkhsdclac

241 Ihfnhsgice Ihcpalvtyn tdtfesmpnp egrytfgasc vtacpynyls tdvgsctlvc

301 plhnqevtae dgtqrcekcs kpcarvcygl gmehlrevra vtsaniqefa gckkifgsla

361 flpesfdgdp asntaplqpe qlqvfetlee itgylyisaw pdslpdlsvf qnlqvirgri

421 Ihngaysltl qglgiswlgl rslrelgsgl alihhnthlc fvhtvpwdql frnphqallh

481 tanrpedecv geglachqlc arghcwgpgp tqcvncsqfl rgqecveecr vlqglpreyv

541 narhclpchp ecqpqngsvt cfgpeadqcv acahykdppf cvarcpsgvk pdlsympiwk

601 fpdeegacqp cpincthscv dlddkgcpae qraspltsii savvgillvv vlgvvfgili

661 krrqqkirky tmrrllqete Ivepltpsga mpnqaqmril ketelrkvkv Igsgafgtvy

721 kgiwipdgen vkipvaikvl rentspkank eildeayvma gvgspyvsrl Igicltstvq

781 Ivtqlmpygc lldhvrenrg rlgsqdllnw cmqiakgmsy ledvrlvhrd laarnvlvks

841 pnhvkitdfg larlldidet eyhadggkvp ikwmalesil rrrfthqsdv wsygvtvwel

901 mtfgakpydg ipareipdll ekgerlpqpp ictidvymim vkcwmidsec rprfrelvse

961 fsrmardpqr fvviqnedlg paspldstfy rslledddmg dlvdaeeylv pqqgffcpdp

1021 apgaggmvhh rhrssstrsg ggdltlglep seeeaprspl apsegagsdv fdgdlgmgaa

1081 kglqslpthd psplqrysed ptvplpsetd gyvapltcsp qpeyvnqpdv rpqppspreg

1141 plpaarpaga tlerpktlsp gkngvvkdvf afggavenpe yltpqggaap qphpppafsp

1201 afdnlyywdq dppergapps tfkgtptaen peylgldvpv

Receptor-tyrosine-protein kinase erbB-2, isoform d NP_001276866.1 (SEQ ID NO: 237)

1 melaalcrwg lllallppga astqvctgtd mklrlpaspe thldmlrhly qgcqvvqgnl

61 eltylptnas Isflqdiqev qgyvliahnq vrqvplqrlr ivrgtqlfed nyalavldng

121 dplnnttpvt gaspgglrel qlrslteilk ggvliqrnpq Icyqdtilwk difhknnqla

181 Itlidtnrsr achpcspmck gsrcwgesse dcqsltrtvc aggcarckgp Iptdccheqc

241 aagctgpkhs dclaclhfnh sgicelhcpa Ivtyntdtfe smpnpegryt fgascvtacp

301 ynylstdvgs ctlvcplhnq evtaedgtqr cekcskpcar vcyglgmehl revravtsan

361 iqefagckki fgslaflpes fdgdpasnta plqpeqlqvf etleeitgyl yisawpdslp

421 dlsvfqnlqv irgrilhnga ysltlqglgi swlglrslre Igsglalihh nthlcfvhtv

481 pwdqlfrnph qallhtanrp edecvgegla chqlcarghc wgpgptqcvn csqflrgqec

541 veecrvlqgl preyvnarhc Ipchpecqpq ngsvtcfgpe adqcvacahy kdppfcvarc

601 psgvkpdlsy mpiwkfpdee gacqpcpinc thscvdlddk gcpaeqrasp Itsiisavvg

661 illvvvlgvv fgilikrrqq kirkytmrrl Iqetelvepl tpsgampnqa qmrilketel

721 rkvkvlgsga fgtvykgiwi pdgenvkipv aikvlrents pkankeilde ayvmagvgsp

781 yvsrllgicl tstvqlvtql mpygclldhv renrgrlgsq dllnwcmqia kgmsyledvr

841 Ivhrdlaarn vlvkspnhvk itdfglarll dideteyhad ggkvpikwma lesilrrrft

901 hqsdvwsygv tvwelmtfga kpydgipare ipdllekger Ipqppictid vymimvkcwm

961 idsecrprfr elvsefsrma rdpqrfvviq nedlgpaspl dstfyrslle dddmgdlvda

1021 eeylvpqqgf fcpdpapgag gmvhhrhrss strnm

Receptor-tyrosine-protein kinase erbB-2, isoform e NP_001276867.1 (SEQ ID NO: 238)

1 mklrlpaspe thldmlrhly qgcqvvqgnl eltylptnas Isflqdiqev qgyvliahnq

61 vrqvplqrlr ivrgtqlfed nyalavldng dplnnttpvt gaspgglrel qlrslteilk

121 ggvliqrnpq Icyqdtilwk difhknnqla Itlidtnrsr achpcspmck gsrcwgesse

181 dcqsltrtvc aggcarckgp Iptdccheqc aagctgpkhs dclaclhfnh sgicelhcpa 241 Ivtyntdtfe smpnpegryt fgascvtacp ynylstdvgs ctlvcplhnq evtaedgtqr 301 cekcskpcar vcyglgmehl revravtsan iqefagckki fgslaflpes fdgdpasnta 361 plqpeqlqvf etleeitgyl yisawpdslp dlsvfqnlqv irgrilhnga ysltlqglgi 421 swlglrslre Igsglalihh nthlcfvhtv pwdqlfrnph qallhtanrp edecvgegla 481 chqlcarghc wgpgptqcvn csqflrgqec veecrvlqgl preyvnarhc Ipchpecqpq 541 ngsvtcfgpe adqcvacahy kdppfcvarc psgvkpdlsy mpiwkfpdee gacqpcpinc 601 ths

Receptor tyrosine-protein kinase erbB-4, isoform JM-a/CVT-1 precursor NP_005226.1 (SEQ ID NO: 239)

1 mkpatglwvw vsllvaagtv qpsdsqsvca gtenklssls dleqqyralr kyyencevvm

61 gnleitsieh nrdlsflrsv revtgyvlva Inqfrylple nlriirgtkl yedryalaif

121 Inyrkdgnfg Iqelglknlt eilnggvyvd qnkflcyadt ihwqdivrnp wpsnltlvst

181 ngssgcgrch ksctgrcwgp tenhcqtltr tvcaeqcdgr cygpyvsdcc hrecaggcsg

241 pkdtdcfacm nfndsgacvt qcpqtfvynp ttfqlehnfn akytygafcv kkcphnfvvd

301 ssscvracps skmeveengi kmckpctdic pkacdgigtg slmsaqtvds snidkfinct

361 kingnliflv tgihgdpyna ieaidpekln vfrtvreitg flniqswppn mtdfsvfsnl

421 vtiggrvlys glsllilkqq gitslqfqsl keisagniyi tdnsnlcyyh tinwttlfst

481 inqrivirdn rkaenctaeg mvcnhlcssd gcwgpgpdqc Iscrrfsrgr iciescnlyd

541 gefrefengs icvecdpqce kmedglltch gpgpdnctkc shfkdgpncv ekcpdglqga

601 nsfifkyadp drechpchpn ctqgcngpts hdciyypwtg hstlpqhart pliaagvigg

661 Ifilvivglt favyvrrksi kkkralrrfl etelvepltp sgtapnqaql rilketelkr

721 vkvlgsgafg tvykgiwvpe getvkipvai kilnettgpk anvefmdeal imasmdhphl

781 vrllgvclsp tiqlvtqlmp hgclleyvhe hkdnigsqll Inwcvqiakg mmyleerrlv

841 hrdlaarnvl vkspnhvkit dfglarlleg dekeynadgg kmpikwmale cihyrkfthq

901 sdvwsygvti welmtfggkp ydgiptreip dllekgerlp qppictidvy mvmvkcwmid

961 adsrpkfkel aaefsrmard pqrylviqgd drmklpspnd skffqnllde edledmmdae

1021 eylvpqafni pppiytsrar idsnrseigh spppaytpms gnqfvyrdgg faaeqgvsvp

1081 yraptstipe apvaqgatae ifddsccngt Irkpvaphvq edsstqrysa dptvfapers

1141 prgeldeegy mtpmrdkpkq eylnpveenp fvsrrkngdl qaldnpeyhn asngppkaed

1201 eyvneplyln tfantlgkae ylknnilsmp ekakkafdnp dywnhslppr stlqhpdylq

1261 eystkyfykq ngrirpivae npeylsefsl kpgtvlpppp yrhrntvv

Receptor tyrosine-protein kinase erbB-4, isoform JM-a/CVT-2 precursor NP_001036064.1 (SEQ ID NO: 240)

1 mkpatglwvw vsllvaagtv qpsdsqsvca gtenklssls dleqqyralr kyyencevvm

61 gnleitsieh nrdlsflrsv revtgyvlva Inqfrylple nlriirgtkl yedryalaif

121 Inyrkdgnfg Iqelglknlt eilnggvyvd qnkflcyadt ihwqdivrnp wpsnltlvst

181 ngssgcgrch ksctgrcwgp tenhcqtltr tvcaeqcdgr cygpyvsdcc hrecaggcsg

241 pkdtdcfacm nfndsgacvt qcpqtfvynp ttfqlehnfn akytygafcv kkcphnfvvd

301 ssscvracps skmeveengi kmckpctdic pkacdgigtg slmsaqtvds snidkfinct

361 kingnliflv tgihgdpyna ieaidpekln vfrtvreitg flniqswppn mtdfsvfsnl

421 vtiggrvlys glsllilkqq gitslqfqsl keisagniyi tdnsnlcyyh tinwttlfst

481 inqrivirdn rkaenctaeg mvcnhlcssd gcwgpgpdqc Iscrrfsrgr iciescnlyd

541 gefrefengs icvecdpqce kmedglltch gpgpdnctkc shfkdgpncv ekcpdglqga

601 nsfifkyadp drechpchpn ctqgcngpts hdciyypwtg hstlpqhart pliaagvigg

661 Ifilvivglt favyvrrksi kkkralrrfl etelvepltp sgtapnqaql rilketelkr

721 vkvlgsgafg tvykgiwvpe getvkipvai kilnettgpk anvefmdeal imasmdhphl

781 vrllgvclsp tiqlvtqlmp hgclleyvhe hkdnigsqll Inwcvqiakg mmyleerrlv

841 hrdlaarnvl vkspnhvkit dfglarlleg dekeynadgg kmpikwmale cihyrkfthq

901 sdvwsygvti welmtfggkp ydgiptreip dllekgerlp qppictidvy mvmvkcwmid

961 adsrpkfkel aaefsrmard pqrylviqgd drmklpspnd skffqnllde edledmmdae

1021 eylvpqafni pppiytsrar idsnrnqfvy rdggfaaeqg vsvpyrapts tipeapvaqg

1081 ataeifddsc cngtlrkpva phvqedsstq rysadptvfa persprgeld eegymtpmrd

1141 kpkqeylnpv eenpfvsrrk ngdlqaldnp eyhnasngpp kaedeyvnep lylntfantl

1201 gkaeylknni Ismpekakka fdnpdywnhs Ipprstlqhp dylqeystky fykqngrirp

1261 ivaenpeyls efslkpgtvl ppppyrhrnt vv

Prolyl endopeptidase FAP, isoform 1 NP_004451.2 (SEQ ID NO: 241)

1 mktwvkivfg vatsavlall vmcivlrpsr vhnseentmr altlkdilng tfsyktffpn

61 wisgqeylhq sadnnivlyn ietgqsytil snrtmksvna snyglspdrq fvylesdysk

121 Iwrysytaty yiydlsngef vrgnelprpi qylcwspvgs klayvyqnni ylkqrpgdpp

181 fqitfngren kifngipdwv yeeemlatky alwwspngkf layaefndtd ipviaysyyg

241 deqyprtini pypkagaknp vvrifiidtt ypayvgpqev pvpamiassd yyfswltwvt 301 dervclqwlk rvqnvsvlsi cdfredwqtw dcpktqehie esrtgwaggf fvstpvfsyd

361 aisyykifsd kdgykhihyi kdtvenaiqi tsgkweaini frvtqdslfy ssnefeeypg

421 rrniyrisig syppskkcvt chlrkercqy ytasfsdyak yyalvcygpg ipistlhdgr

481 tdqeikilee nkelenalkn iqlpkeeikk levdeitlwy kmilppqfdr skkyplliqv

541 yggpcsqsvr svfavnwisy laskegmvia Ivdgrgtafq gdkllyavyr klgvyevedq

601 itavrkfiem gfidekriai wgwsyggyvs slalasgtgl fkcgiavapv ssweyyasvy

661 terfmglptk ddnlehykns tvmaraeyfr nvdyllihgt addnvhfqns aqiakalvna

721 qvdfqamwys dqnhglsgls tnhlythmth flkqcfslsd

Prolyl endopeptidase FAP, isoform 2 NP_001278736.1 (SEQ ID NO: 242)

1 mktwvkivfg vatsavlall vmcivlrpsr vhnseentmr altlkdilng tfsyktffpn

61 wisgqeylhq sadnnivlyn ietgqsytil snrtmlwrys ytatyyiydl sngefvrgne

121 Iprpiqylcw spvgsklayv yqnniylkqr pgdppfqitf ngrenkifng ipdwvyeeem

181 latkyalwws pngkflayae fndtdipvia ysyygdeqyp rtinipypka gaknpvvrif

241 iidttypayv gpqevpvpam iassdyyfsw Itwvtdervc Iqwlkrvqnv svlsicdfre

301 dwqtwdcpkt qehieesrtg waggffvstp vfsydaisyy kifsdkdgyk hihyikdtve

361 naiqitsgkw eainifrvtq dslfyssnef eeypgrrniy risigsypps kkcvtchlrk

421 ercqyytasf sdyakyyalv cygpgipist Ihdgrtdqei kileenkele nalkniqlpk

481 eeikklevde itlwykmilp pqfdrskkyp lliqvyggpc sqsvrsvfav nwisylaske

541 gmvialvdgr gtafqgdkll yavyrklgvy evedqitavr kfiemgfide kriaiwgwsy

601 ggyvsslala sgtglfkcgi avapvsswey yasvyterfm glptkddnle hyknstvmar

661 aeyfrnvdyl lihgtaddnv hfqnsaqiak alvnaqvdfq amwysdqnhg Isglstnhly

721 thmthflkqc fslsd

Glutamate carboxypeptidase 2, isoform 1 NP_004467.1 (SEQ ID NO: 243)

1 mwnllhetds avatarrprw Icagalvlag gffllgflfg wfikssneat nitpkhnmka

61 fldelkaeni kkflynftqi phlagteqnf qlakqiqsqw kefgldsvel ahydvllsyp

121 nkthpnyisi inedgneifn tslfeppppg yenvsdivpp fsafspqgmp egdlvyvnya

181 rtedffkler dmkincsgki viarygkvfr gnkvknaqla gakgvilysd padyfapgvk

241 sypdgwnlpg ggvqrgniln Ingagdpltp gypaneyayr rgiaeavglp sipvhpigyy

301 daqkllekmg gsappdsswr gslkvpynvg pgftgnfstq kvkmhihstn evtriynvig

361 tlrgavepdr yvilgghrds wvfggidpqs gaavvheivr sfgtlkkegw rprrtilfas

421 wdaeefgllg stewaeensr llqergvayi nadssiegny tlrvdctplm yslvhnltke

481 Ikspdegfeg kslyeswtkk spspefsgmp risklgsgnd fevffqrlgi asgrarytkn

541 wetnkfsgyp lyhsvyetye Ivekfydpmf kyhltvaqvr ggmvfelans ivlpfdcrdy

601 avvlrkyadk iysismkhpq emktysvsfd slfsavknft eiaskfserl qdfdksnpiv

661 Irmmndqlmf lerafidplg Ipdrpfyrhv iyapsshnky agesfpgiyd alfdieskvd

721 pskawgevkr qiyvaaftvq aaaetlseva

Glutamate carboxypeptidase 2, isoform 2 NP_001014986.1 (SEQ ID NO: 244)

1 mwnllhetds avatarrprw Icagalvlag gffllgflfg wfikssneat nitpkhnmka

61 fldelkaeni kkflynftqi phlagteqnf qlakqiqsqw kefgldsvel ahydvllsyp

121 nkthpnyisi inedgneifn tslfeppppg yenvsdivpp fsafspqgmp egdlvyvnya

181 rtedffkler dmkincsgki viarygkvfr gnkvknaqla gakgvilysd padyfapgvk

241 sypdgwnlpg ggvqrgniln Ingagdpltp gypaneyayr rgiaeavglp sipvhpigyy

301 daqkllekmg gsappdsswr gslkvpynvg pgftgnfstq kvkmhihstn evtriynvig

361 tlrgavepdr yvilgghrds wvfggidpqs gaavvheivr sfgtlkkegw rprrtilfas

421 wdaeefgllg stewaeensr llqergvayi nadssiegny tlrvdctplm yslvhnltke

481 Ikspdegfeg kslyeswtkk spspefsgmp risklgsgnd fevffqrlgi asgrarytkn

541 wetnkfsgyp lyhsvyetye Ivekfydpmf kyhltvaqvr ggmvfelans ivlpfdcrdy

601 avvlrkyadk iysismkhpq emktysvsfd slfsavknft eiaskfserl qdfdkskhvi

661 yapsshnkya gesfpgiyda Ifdieskvdp skawgevkrq iyvaaftvqa aaetlseva

Glutamate carboxypeptidase 2, isoform 3 NP_001180400.1 (SEQ ID NO: 245)

1 mtagssyplf laayactgcl aerlgwfiks sneatnitpk hnmkafldel kaenikkfly

61 nftqiphlag teqnfqlakq iqsqwkefgl dsvelahydv llsypnkthp nyisiinedg

121 neifntslfe ppppgyenvs divppfsafs pqgmpegdlv yvnyartedf fklerdmkin

181 csgkiviary gkvfrgnkvk naqlagakgv ilysdpadyf apgvksypdg wnlpgggvqr

241 gnilnlngag dpltpgypan eyayrrgiae avglpsipvh pigyydaqkl lekmggsapp

301 dsswrgslkv pynvgpgftg nfstqkvkmh ihstnevtri ynvigtlrga vepdryvilg

361 ghrdswvfgg idpqsgaavv heivrsfgtl kkegwrprrt ilfaswdaee fgllgstewa

421 eensrllqer gvayinadss iegnytlrvd ctplmyslvh nltkelkspd egfegkslye

481 swtkkspspe fsgmpriskl gsgndfevff qrlgiasgra rytknwetnk fsgyplyhsv

541 yetyelvekf ydpmfkyhlt vaqvrggmvf elansivlpf dcrdyavvlr kyadkiysis

601 mkhpqemkty svsfdslfsa vknfteiask fserlqdfdk snpivlrmmn dqlmfleraf 661 idplglpdrp fyrhviyaps shnkyagesf pgiydalfdi eskvdpskaw gevkrqiyva 721 aftvqaaaet Iseva

Glutamate carboxypeptidase 2, isoform 4 NP_001180401.1 (SEQ ID NO: 246)

1 mtagssyplf laayactgcl aerlgwfiks sneatnitpk hnmkafldel kaenikkfly

61 nftqiphlag teqnfqlakq iqsqwkefgl dsvelahydv llsypnkthp nyisiinedg

121 neifntslfe ppppgyenvs divppfsafs pqgmpegdlv yvnyartedf fklerdmkin

181 csgkiviary gkvfrgnkvk naqlagakgv ilysdpadyf apgvksypdg wnlpgggvqr

241 gnilnlngag dpltpgypan eyayrrgiae avglpsipvh pigyydaqkl lekmggsapp

301 dsswrgslkv pynvgpgftg nfstqkvkmh ihstnevtri ynvigtlrga vepdryvilg

361 ghrdswvfgg idpqsgaavv heivrsfgtl kkegwrprrt ilfaswdaee fgllgstewa

421 eensrllqer gvayinadss iegnytlrvd ctplmyslvh nltkelkspd egfegkslye

481 swtkkspspe fsgmpriskl gsgndfevff qrlgiasgra rytknwetnk fsgyplyhsv

541 yetyelvekf ydpmfkyhlt vaqvrggmvf elansivlpf dcrdyavvlr kyadkiysis

601 mkhpqemkty svsfdslfsa vknfteiask fserlqdfdk skhviyapss hnkyagesfp

661 giydalfdie skvdpskawg evkrqiyvaa ftvqaaaetl seva

Glutamate carboxypeptidase 2, isoform 5 NP_001180402.1 (SEQ ID NO: 247)

1 mggsappdss wrgslkvpyn vgpgftgnfs tqkvkmhihs tnevtriynv igtlrgavep

61 dryvilgghr dswvfggidp qsgaavvhei vrsfgtlkke gwrprrtilf aswdaeefgl

121 Igstewaeen srllqergva yinadssieg nytlrvdctp Imyslvhnlt kelkspdegf

181 egkslyeswt kkspspefsg mprisklgsg ndfevffqrl giasgraryt knwetnkfsg

241 yplyhsvyet yelvekfydp mfkyhltvaq vrggmvfela nsivlpfdcr dyavvlrkya

301 dkiysismkh pqemktysvs fdslfsavkn fteiaskfse rlqdfdksnp ivlrmmndql

361 mflerafidp Iglpdrpfyr hviyapsshn kyagesfpgi ydalfdiesk vdpskawgev

421 krqiyvaaft vqaaaetlse va

Glutamate carboxypeptidase 2, isoform 6 NP_001338165.1 (SEQ ID NO: 248)

1 mkafldelka enikkflynf tqiphlagte qnfqlakqiq sqwkefglds velahydvll

61 sypnkthpny isiinedgne ifntslfepp ppgyenvsdi vppfsafspq gmpegdlvyv

121 nyartedffk lerdmkincs gkiviarygk vfrgnkvkna qlagakgvil ysdpadyfap

181 gvksypdgwn Ipgggvqrgn ilnlngagdp Itpgypaney ayrrgiaeav glpsipvhpi

241 gyydaqklle kmggsappds swrgslkvpy nvgpgftgnf stqkvkmhih stnevtriyn

301 vigtlrgave pdryvilggh rdswvfggid pqsgaavvhe ivrsfgtlkk egwrprrtil

361 faswdaeefg llgstewaee nsrllqergv ayinadssie gnytlrvdct plmyslvhnl

421 tkelkspdeg fegkslyesw tkkspspefs gmprisklgs gndfevffqr Igiasgrary

481 tknwetnkfs gyplyhsvye tyelvekfyd pmfkyhltva qvrggmvfel ansivlpfdc

541 rdyavvlrky adkiysismk hpqemktysv sfdslfsavk nfteiaskfs erlqdfdksk

601 hviyapsshn kyagesfpgi ydalfdiesk vdpskawgev krqiyvaaft vqaaaetlse

661 va

Fos-related antigen 1, isoform 1 NP_005429.1 (SEQ ID NO: 249)

1 mfrdfgepgp ssgngggygg paqppaaaqa aqqkfhlvps intmsgsqel qwmvqphflg

61 pssyprplty pqysppqprp gviralgppp gvrrrpceqi speeeerrrv rrernklaaa

121 kcrnrrkelt dflqaetdkl edeksglqre ieelqkqker lelvleahrp ickipegake

181 gdtgstsgts sppapcrpvp cislspgpvl epealhtptl mttpsltpft pslvftypst

241 pepcasahrk sssssgdpss dplgsptlla 1

Fos-related antigen 1, isoform 2 NP_001287773.1 (SEQ ID NO: 250)

1 mfrdfgepgp ssgngggygg paqppaaaqa aqqkfhlvps intmsgsqel qwmvqphflg

61 pssyprplty pqysppqprp gviralgppp gvrrrpceqe tdkledeksg Iqreieelqk

121 qkerlelvle ahrpickipe gakegdtgst sgtssppapc rpvpcislsp gpvlepealh

181 tptlmttpsl tpftpslvft ypstpepcas ahrksssssg dpssdplgsp tllal

Fos-related antigen 1, isoform 3 NP_001287784.1 (SEQ ID NO: 251)

1 mfrdfgepgp ssgngggygg paqppaaaqa aqqkfhlvps intmsgsqel qwmvqphflg

61 pssyprplty pqysppqprp gviralgppp gvrrrpceqp ggrgappska raeqagcgqv

121 qepeegtdrl paggd

Fos-related antigen 1, isoform 4 NP_001287785.1 (SEQ ID NO: 252)

1 mfrdfgepgp ssgngggygg paqppaaaqa aqqispeeee rrrvrrernk laaakcrnrr

61 keltdflqae tdkledeksg Iqreieelqk qkerlelvle ahrpickipe gakegdtgst

121 sgtssppapc rpvpcislsp gpvlepealh tptlmttpsl tpftpslvft ypstpepcas

181 ahrksssssg dpssdplgsp tllal

Fos-related antigen 1, isoform 5 NP_001287786.1 (SEQ ID NO: 253)

1 mfrdfgepgp ssgngggygg paqppaaaqa aqqetdkled eksglqreie elqkqkerle

61 Ivleahrpic kipegakegd tgstsgtssp papcrpvpci slspgpvlep ealhtptlmt

121 tpsltpftps Ivftypstpe pcasahrkss sssgdpssdp Igsptllal G antigen 1 NP_001035753.1 (SEQ ID NO: 254)

1 mswrgrstyy wprprryvqp pemigpmrpe qfsdevepat peegepatqr qdpaaaqege

61 degasagqgp kpeadsqeqg hpqtgceced gpdgqemdpp npeevktpee gegqsqc

G antigen 121 NP_001465.1 (SEQ ID NO: 255)

1 mswrgrstyy wprprryvqp pemigpmrpe qfsdevepat peegepatqr qdpaaaqege

61 degasagqgp kpeadsqeqg hpqtgceced gpdgqemdpp npeevktpee gekqsqc

Galectin-1 NP_002296.1 (SEQ ID NO: 256)

1 macglvasnl nlkpgeclrv rgevapdaks fvlnlgkdsn nlclhfnprf nahgdantiv

61 cnskdggawg teqreavfpf qpgsvaevci tfdqanltvk Ipdgyefkfp nrlnleainy

121 maadgdfkik cvafd

Galectin-3 isoform 1 NP_002297.2 (SEQ ID NO: 257)

1 madnfslhda Isgsgnpnpq gwpgawgnqp agaggypgas ypgaypgqap pgaypgqapp

61 gaypgapgay pgapapgvyp gppsgpgayp ssgqpsatga ypatgpygap agplivpynl

121 plpggvvprm litilgtvkp nanrialdfq rgndvafhfn prfnennrrv ivcntkldnn

181 wgreerqsvf pfesgkpfki qvlvepdhfk vavndahllq ynhrvkklne isklgisgdi

241 dltsasytmi

Galectin-3, isoform 3 NP_001344607.1 (SEQ ID NO: 258)

1 mhsktpcgcf kpwkmadnfs Ihdalsgsgn pnpqgwpgaw gnqpagaggy pgasypgayp

61 gqappgaypg qappgaypga pgaypgapap gvypgppsgp gaypssgqps atgaypatgp

121 ygapagpliv pynlplpggv vprmlitilg tvkpnanria Idfqrgndva fhfnprfnen

181 nrrvivcntk Idnnwgreer qsvfpfesgk pfkiqvlvep dhfkvavnda hllqynhrvk

241 klneisklgi sgdidltsas ytmi

Galectin-9 short NP_002299.2 (SEQ ID NO: 259)

1 mafsgsqapy Ispavpfsgt iqgglqdglq itvngtvlss sgtrfavnfq tgfsgndiaf

61 hfnprfedgg yvvcntrqng swgpeerkth mpfqkgmpfd Icflvqssdf kvmvngilfv

121 qyfhrvpfhr vdtisvngsv qlsyisfqpp gvwpanpapi tqtvihtvqs apgqmfstpa

181 ippmmyphpa ypmpfittil gglypsksil Isgtvlpsaq rfhinlcsgn hiafhlnprf

241 denavvrntq idnswgseer slprkmpfvr gqsfsvwilc eahclkvavd gqhlfeyyhr

301 Irnlptinrl evggdiqlth vqt

Galectin-9 long NP_033665.1 (SEQ ID NO: 260)

1 mafsgsqapy Ispavpfsgt iqgglqdglq itvngtvlss sgtrfavnfq tgfsgndiaf

61 hfnprfedgg yvvcntrqng swgpeerkth mpfqkgmpfd Icflvqssdf kvmvngilfv

121 qyfhrvpfhr vdtisvngsv qlsyisfqnp rtvpvqpafs tvpfsqpvcf pprprgrrqk

181 ppgvwpanpa pitqtvihtv qsapgqmfst paippmmyph paypmpfitt ilgglypsks

241 illsgtvlps aqrfhinlcs gnhiafhlnp rfdenavvrn tqidnswgse erslprkmpf

301 vrgqsfsvwi Iceahclkva vdgqhlfeyy hrlrnlptin rlevggdiql thvqt

Galectin-9 isoform 3 NP_001317092.1 (SEQ ID NO: 261)

1 mafsgsqapy Ispavpfsgt iqgglqdglq itvngtvlss sgtrfavnfq tgfsgndiaf

61 hfnprfedgg yvvcntrqng swgpeerkth mpfqkgmpfd Icflvqssdf kvmvngilfv

121 qyfhrvpfhr vdtisvngsv qlsyisfqpp gvwpanpapi tqtvihtvqs apgqmfstpa

181 ippmmyphpa ypmpfittil gglypsksil Isgtvlpsaq rcgscvklta srwpwmvstc

241 Inttia

Premelanosome protein, isoform 1 preprotein NP_001186983.1 (SEQ ID NO: 262)

1 mdlvlkrcll hlavigalla vgatkvprnq dwlgvsrqlr tkawnrqlyp ewteaqrldc

61 wrggqvslkv sndgptliga nasfsialnf pgsqkvlpdg qviwvnntii ngsqvwggqp

121 vypqetddac ifpdggpcps gswsqkrsfv yvwktwgqyw qvlggpvsgl sigtgramlg

181 thtmevtvyh rrgsrsyvpl ahsssaftit dqvpfsvsvs qlraldggnk hflrnqpltf

241 alqlhdpsgy laeadlsytw dfgdssgtli sralvvthty lepgpvtaqv vlqaaiplts

301 cgsspvpgtt dghrptaeap nttagqvptt evvgttpgqa ptaepsgtts vqvpttevis

361 tapvqmptae stgmtpekvp vsevmgttla emstpeatgm tpaevsivvl sgttaaqvtt

421 tewvettare Ipipepegpd assimstesi tgslgplldg tatlrlvkrq vpldcvlyry

481 gsfsvtldiv qgiesaeilq avpsgegdaf eltvscqggl pkeacmeiss pgcqppaqrl

541 cqpvlpspac qlvlhqilkg gsgtyclnvs ladtnslavv stqlimpvpg illtgqeagl

601 gqvplivgil Ivlmavvlas liyrrrlmkq dfsvpqlphs sshwlrlpri fcscpigens

661 pllsgqqv

Premelanosome protein, isoform 2 precursor NP_001186982.1 (SEQ ID NO: 263)

1 mdlvlkrcll hlavigalla vgatkgsqvw ggqpvypqet ddacifpdgg pcpsgswsqk

61 rsfvyvwktw gqywqvlggp vsglsigtgr amlgthtmev tvyhrrgsrs yvplahsssa

121 ftitdqvpfs vsvsqlrald ggnkhflrnq pltfalqlhd psgylaeadl sytwdfgdss

181 gtlisralvv thtylepgpv taqvvlqaai pltscgsspv pgttdghrpt aeapnttagq

241 vpttevvgtt pgqaptaeps gttsvqvptt evistapvqm ptaestgmtp ekvpvsevmg 301 ttlaemstpe atgmtpaevs ivvlsgttaa qvtttewvet tarelpipep egpdassims

361 tesitgslgp lldgtatlrl vkrqvpldcv lyrygsfsvt Idivqgiesa eilqavpsge

421 gdafeltvsc qgglpkeacm eisspgcqpp aqrlcqpvlp spacqlvlhq ilkggsgtyc

481 Invsladtns lavvstqlim pgqeaglgqv plivgillvl mavvlasliy rrrlmkqdfs

541 vpqlphsssh wlrlprifcs cpigenspll sgqqv

Premelanosome protein, isoform 3 preprotein NP_008859.1 (SEQ ID NO: 264)

1 mdlvlkrcll hlavigalla vgatkvprnq dwlgvsrqlr tkawnrqlyp ewteaqrldc

61 wrggqvslkv sndgptliga nasfsialnf pgsqkvlpdg qviwvnntii ngsqvwggqp

121 vypqetddac ifpdggpcps gswsqkrsfv yvwktwgqyw qvlggpvsgl sigtgramlg

181 thtmevtvyh rrgsrsyvpl ahsssaftit dqvpfsvsvs qlraldggnk hflrnqpltf

241 alqlhdpsgy laeadlsytw dfgdssgtli sralvvthty lepgpvtaqv vlqaaiplts

301 cgsspvpgtt dghrptaeap nttagqvptt evvgttpgqa ptaepsgtts vqvpttevis

361 tapvqmptae stgmtpekvp vsevmgttla emstpeatgm tpaevsivvl sgttaaqvtt

421 tewvettare Ipipepegpd assimstesi tgslgplldg tatlrlvkrq vpldcvlyry

481 gsfsvtldiv qgiesaeilq avpsgegdaf eltvscqggl pkeacmeiss pgcqppaqrl

541 cqpvlpspac qlvlhqilkg gsgtyclnvs ladtnslavv stqlimpgqe aglgqvpliv

601 gillvlmavv lasliyrrrl mkqdfsvpql phssshwlrl prifcscpig enspllsgqq

661 v

Premelanosome protein, isoform 4 preprotein NP_001307050.1 (SEQ ID NO: 265)

1 mdlvlkrcll hlavigalla vgatkvprnq dwlgvsrqlr tkawnrqlyp ewteaqrldc

61 wrggqvslkv sndgptliga nasfsialnf pgsqkvlpdg qviwvnntii ngsqvwggqp

121 vypqetddac ifpdggpcps gswsqkrsfv yvwktwgqyw qvlggpvsgl sigtgramlg

181 thtmevtvyh rrgsrsyvpl ahsssaftit dqvpfsvsvs qlraldggnk hflrnqpltf

241 alqlhdpsgy laeadlsytw dfgdssgtli sralvvthty lepgpvtaqv vlqaaiplts

301 cgsspvpgtt dghrptaeap nttagqvptt evvgttpgqa ptaepsgtts vqvpttevis

361 tapvqmptae staaqvttte wvettarelp ipepegpdas simstesitg slgplldgta

421 tlrlvkrqvp Idcvlyrygs fsvtldivqg iesaeilqav psgegdafel tvscqgglpk

481 eacmeisspg cqppaqrlcq pvlpspacql vlhqilkggs gtyclnvsla dtnslavvst

541 qlimpvpgil Itgqeaglgq vplivgillv Imavvlasli yrrrlmkqdf svpqlphsss

601 hwlrlprifc scpigenspl Isgqqv

Premelanosome protein, isoform 5 preprotein NP_001307051.1 (SEQ ID NO: 266)

1 mdlvlkrcll hlavigalla vgatkvprnq dwlgvsrqlr tkawnrqlyp ewteaqrldc

61 wrggqvslkv sndgptliga nasfsialnf pgsqkvlpdg qviwvnntii ngsqvwggqp

121 vypqetddac ifpdggpcps gswsqkrsfv yvwktwgqyw qvlggpvsgl sigtgramlg

181 thtmevtvyh rrgsrsyvpl ahsssaftit dqvpfsvsvs qlraldggnk hflrnqpltf

241 alqlhdpsgy laeadlsytw dfgdssgtli sralvvthty lepgpvtaqv vlqaaiplts

301 cgsspvpgtt dghrptaeap nttagqvptt evvgttpgqa ptaepsgtts vqvpttevis

361 tapvqmptae staaqvttte wvettarelp ipepegpdas simstesitg slgplldgta

421 tlrlvkrqvp Idcvlyrygs fsvtldivqg iesaeilqav psgegdafel tvscqgglpk

481 eacmeisspg cqppaqrlcq pvlpspacql vlhqilkggs gtyclnvsla dtnslavvst

541 qlimpgqeag Igqvplivgi llvlmavvla sliyrrrlmk qdfsvpqlph ssshwlrlpr

601 ifcscpigen spllsgqqv

Glutamate receptor ionotropic, NMDA 2A, isoform 1 precursor NP_000824.1, NP_001127879.1 (SEQ ID NO: 267)

1 mgrvgywtll vlpallvwrg papsaaaekg ppalniavml ghshdvtere Irtlwgpeqa

61 aglpldvnvv allmnrtdpk slithvcdlm sgarihglvf gddtdqeava qmldfissht

121 fvpilgihgg asmimadkdp tstffqfgas iqqqatvmlk imqdydwhvf slvttifpgy

181 refisfvktt vdnsfvgwdm qnvitldtsf edaktqvqlk kihssvilly cskdeavlil

241 searslgltg ydffwivpsl vsgntelipk efpsglisvs yddwdyslea rvrdgigilt

301 taassmlekf syipeakasc ygqmerpevp mhtlhpfmvn vtwdgkdlsf teegyqvhpr

361 Ivvivlnkdr ewekvgkwen htlslrhavw pryksfsdce pddnhlsivt leeapfvive

421 didpltetcv rntvpcrkfv kinnstnegm nvkkcckgfc idilkklsrt vkftydlylv

481 tngkhgkkvn nvwngmigev vyqravmavg sltineerse vvdfsvpfve tgisvmvsrs

541 ngtvspsafl epfsasvwvm mfvmllivsa iavfvfeyfs pvgynrnlak gkaphgpsft

601 igkaiwllwg Ivfnnsvpvq npkgttskim vsvwaffavi flasytanla afmiqeefvd

661 qvtglsdkkf qrphdysppf rfgtvpngst ernirnnypy mhqymtkfnq kgvedalvsl

721 ktgkldafiy daavlnykag rdegcklvti gsgyifattg ygialqkgsp wkrqidlall

781 qfvgdgemee letlwltgic hneknevmss qldidnmagv fymlaaamal slitfiwehl

841 fywklrfcft gvcsdrpgll fsisrgiysc ihgvhieekk kspdfnltgs qsnmlkllrs

901 aknissmsnm nssrmdspkr aadfiqrgsl imdmvsdkgn Imysdnrsfq gkesifgdnm

961 nelqtfvanr qkdnlnnyvf qgqhpltlne snpntvevav steskansrp rqlwkksvds 1021 irqdslsqnp vsqrdeatae nrthslkspr ylpeemahsd isetsnratc hrepdnsknh

1081 ktkdnfkrsv askypkdcse vertylktks ssprdkiyti dgekepgfhl dppqfvenvt

1141 Ipenvdfpdp yqdpsenfrk gdstlpmnrn plhneeglsn ndqyklyskh ftlkdkgsph

1201 setseryrqn sthcrsclsn mptysghftm rspfkcdacl rmgnlydide dqmlqetgnp

1261 atgeqvyqqd waqnnalqlq knklrisrqh sydnivdkpr eldlsrpsrs islkdrerll

1321 egnfygslfs vpssklsgkk sslfpqgled skrsksllpd htsdnpflhs hrddqrlvig

1381 rcpsdpykhs Ipsqavndsy Irsslrstas ycsrdsrghn dvyisehvmp yaanknnmys

1441 tprvlnscsn rrvykkmpsi esdv

Glutamate receptor ionotropic,NMDA 2A, isoform 2 precursor NP_001127880.1 (SEQ ID NO: 268)

1 mgrvgywtll vlpallvwrg papsaaaekg ppalniavml ghshdvtere Irtlwgpeqa

61 aglpldvnvv allmnrtdpk slithvcdlm sgarihglvf gddtdqeava qmldfissht

121 fvpilgihgg asmimadkdp tstffqfgas iqqqatvmlk imqdydwhvf slvttifpgy

181 refisfvktt vdnsfvgwdm qnvitldtsf edaktqvqlk kihssvilly cskdeavlil

241 searslgltg ydffwivpsl vsgntelipk efpsglisvs yddwdyslea rvrdgigilt

301 taassmlekf syipeakasc ygqmerpevp mhtlhpfmvn vtwdgkdlsf teegyqvhpr

361 Ivvivlnkdr ewekvgkwen htlslrhavw pryksfsdce pddnhlsivt leeapfvive

421 didpltetcv rntvpcrkfv kinnstnegm nvkkcckgfc idilkklsrt vkftydlylv

481 tngkhgkkvn nvwngmigev vyqravmavg sltineerse vvdfsvpfve tgisvmvsrs

541 ngtvspsafl epfsasvwvm mfvmllivsa iavfvfeyfs pvgynrnlak gkaphgpsft

601 igkaiwllwg Ivfnnsvpvq npkgttskim vsvwaffavi flasytanla afmiqeefvd

661 qvtglsdkkf qrphdysppf rfgtvpngst ernirnnypy mhqymtkfnq kgvedalvsl

721 ktgkldafiy daavlnykag rdegcklvti gsgyifattg ygialqkgsp wkrqidlall

781 qfvgdgemee letlwltgic hneknevmss qldidnmagv fymlaaamal slitfiwehl

841 fywklrfcft gvcsdrpgll fsisrgiysc ihgvhieekk kspdfnltgs qsnmlkllrs

901 aknissmsnm nssrmdspkr aadfiqrgsl imdmvsdkgn Imysdnrsfq gkesifgdnm

961 nelqtfvanr qkdnlnnyvf qgqhpltlne snpntvevav steskansrp rqlwkksvds

1021 irqdslsqnp vsqrdeatae nrthslkspr ylpeemahsd isetsnratc hrepdnsknh

1081 ktkdnfkrsv askypkdcse vertylktks ssprdkiyti dgekepgfhl dppqfvenvt

1141 Ipenvdfpdp yqdpsenfrk gdstlpmnrn plhneeglsn ndqyklyskh ftlkdkgsph

1201 setseryrqn sthcrsclsn mptysghftm rspfkcdacl rmgnlydide dqmlqetgmt

1261 nawllgdapr tltntrchpr r

Metabotropic glutamate receptor 3 precursor NP_000831.2 (SEQ ID NO: 269)

1 mkmltrlqvl tlalfskgfl Islgdhnflr reikiegdlv Igglfpinek gtgteecgri

61 nedrgiqrle amlfaidein kddyllpgvk Igvhildtcs rdtyaleqsl efvrasltkv

121 deaeymcpdg syaiqenipl liagviggsy ssvsiqvanl Irlfqipqis yastsaklsd

181 ksrydyfart vppdfyqaka maeilrffnw tyvstvaseg dygetgieaf eqearlrnic

241 iataekvgrs nirksydsvi rellqkpnar vvvlfmrsdd sreliaaasr anasftwvas

301 dgwgaqesii kgsehvayga itlelasqpv rqfdryfqsl npynnhrnpw frdfweqkfq

361 cslqnkrnhr rvcdkhlaid ssnyeqeski mfvvnavyam ahalhkmqrt Icpnttklcd

421 amkildgkkl ykdyllkinf tapfnpnkda dsivkfdtfg dgmgrynvfn fqnvggkysy

481 Ikvghwaetl sldvnsihws rnsvptsqcs dpcapnemkn mqpgdvccwi cipcepyeyl

541 adeftcmdcg sgqwptadlt gcydlpedyi rwedawaigp vtiaclgfmc tcmvvtvfik

601 hnntplvkas grelcyillf gvglsycmtf ffiakpspvi calrrlglgs sfaicysall

661 tktnciarif dgvkngaqrp kfispssqvf iclglilvqi vmvsvwlile apgtrrytla

721 ekretvilkc nvkdssmlis Itydvilvil ctvyafktrk cpenfneakf igftmyttci

781 iwlaflpify vtssdyrvqt ttmcisvsls gfvvlgclfa pkvhiilfqp qknvvthrlh

841 Inrfsvsgtg ttysqssast yvptvcngre vldsttssl

HPV E6 concoprotein, NP_041325.1 (SEQ ID NO: 270)

1 mhqkrtamfq dpqerprklp qlctelqtti hdiilecvyc kqqllrrevy dfafrdlciv 61 yrdgnpyavc dkclkfyski seyrhycysl ygttleqqyn kplcdllirc incqkplcpe 121 ekqrhldkkq rfhnirgrwt grcmsccrss rtrretql

HPV E7 Oncoprotein, NP_041326.1 (SEQ ID NO: 271)

1 mhgdtptlhe ymldlqpett dlycyeqlnd sseeedeidg pagqaepdra hynivtfcck 61 cdstlrlcvq sthvdirtle dllmgtlgiv cpicsqkp

GTPase HRas, isoform 1 NP_001123914.1, NP_005334.1 (SEQ ID NO: 272)

1 mteyklvvvg aggvgksalt iqliqnhfvd eydptiedsy rkqvvidget clldildtag

61 qeeysamrdq ymrtgegflc vfainntksf edihqyreqi krvkdsddvp mvlvgnkcdl

121 aartvesrqa qdlarsygip yietsaktrq gvedafytlv reirqhklrk Inppdesgpg

181 cmsckcvls

GTPase HRas, isoform 3 NP 001304983.1 (SEQ ID NO: 273) 1 mtcpwcwwgt svtwlhalwn Igrlrtspea tasptsrprp rpgraaalal apapgpsgtp 61 rdpcdpaapr agvedafytl vreirqhklr klnppdesgp gcmsckcvls

GTPase HRaSj isoform 2 NP_789765.1 (SEQ ID NO: 274)

1 mteyklvvvg aggvgksalt iqliqnhfvd eydptiedsy rkqvvidget clldildtag 61 qeeysamrdq ymrtgegflc vfainntksf edihqyreqi krvkdsddvp mvlvgnkcdl 121 aartvesrqa qdlarsygip yietsaktrq gsrsgsssss gtlwdppgpm

Vascular endothelial growth factor receptor 2 precursor NP_002244.1 (SEQ ID NO: 275)

1 mqskvllava Iwlcvetraa svglpsvsld Iprlsiqkdi Itikanttlq itcrgqrdld

61 wlwpnnqsgs eqrvevtecs dglfcktlti pkvigndtga ykcfyretdl asviyvyvqd

121 yrspfiasvs dqhgvvyite nknktvvipc Igsisnlnvs Icarypekrf vpdgnriswd

181 skkgftipsy misyagmvfc eakindesyq simyivvvvg yriydvvlsp shgielsvge

241 klvlnctart elnvgidfnw eypsskhqhk klvnrdlktq sgsemkkfls tltidgvtrs

301 dqglytcaas sglmtkknst fvrvhekpfv afgsgmeslv eatvgervri pakylgyppp

361 eikwykngip lesnhtikag hvltimevse rdtgnytvil tnpiskekqs hvvslvvyvp

421 pqigekslis pvdsyqygtt qtltctvyai ppphhihwyw qleeecanep sqavsvtnpy

481 pceewrsved fqggnkievn knqfaliegk nktvstlviq aanvsalykc eavnkvgrge

541 rvisfhvtrg peitlqpdmq pteqesvslw ctadrstfen Itwyklgpqp Ipihvgelpt

601 pvcknldtlw klnatmfsns tndilimelk naslqdqgdy vclaqdrktk krhcvvrqlt

661 vlervaptit gnlenqttsi gesievscta sgnpppqimw fkdnetlved sgivlkdgnr

721 nltirrvrke deglytcqac svlgcakvea ffiiegaqek tnleiiilvg taviamffwl

781 llviilrtvk ranggelktg ylsivmdpde Ipldehcerl pydaskwefp rdrlklgkpl

841 grgafgqvie adafgidkta tcrtvavkml kegathsehr almselkili highhlnvvn

901 llgactkpgg plmvivefck fgnlstylrs krnefvpykt kgarfrqgkd yvgaipvdlk

961 rrldsitssq ssassgfvee kslsdveeee apedlykdfl tlehlicysf qvakgmefla

1021 srkcihrdla arnillsekn vvkicdfgla rdiykdpdyv rkgdarlplk wmapetifdr

1081 vytiqsdvws fgvllweifs Igaspypgvk ideefcrrlk egtrmrapdy ttpemyqtml

1141 dcwhgepsqr ptfselvehl gnllqanaqq dgkdyivlpi setlsmeeds glslptspvs

1201 cmeeeevcdp kfhydntagi sqylqnskrk srpvsvktfe dipleepevk vipddnqtds

1261 gmvlaseelk tledrtklsp sfggmvpsks resvasegsn qtsgyqsgyh sddtdttvys

1321 seeaellkli eigvqtgsta qilqpdsgtt Issppv

Mast/stem cell growth acor receptor KIT, isoform 1 precursor NP_000213.1 (SEQ ID NO: 276)

1 mrgargawdf Icvlllllrv qtgssqpsvs pgepsppsih pgksdlivrv gdeirllctd

61 pgfvkwtfei Idetnenkqn ewitekaeat ntgkytctnk hglsnsiyvf vrdpaklflv

121 drslygkedn dtlvrcpltd pevtnyslkg cqgkplpkdl rfipdpkagi miksvkrayh

181 rlclhcsvdq egksvlsekf ilkvrpafka vpvvsvskas yllregeeft vtctikdvss

241 svystwkren sqtklqekyn swhhgdfnye rqatltissa rvndsgvfmc yanntfgsan

301 vtttlevvdk gfinifpmin ttvfvndgen vdliveyeaf pkpehqqwiy mnrtftdkwe

361 dypksenesn iryvselhlt rlkgteggty tflvsnsdvn aaiafnvyvn tkpeiltydr

421 Ivngmlqcva agfpeptidw yfcpgteqrc sasvlpvdvq tlnssgppfg klvvqssids

481 safkhngtve ckayndvgkt sayfnfafkg nnkeqihpht Iftplligfv ivagmmciiv

541 miltykylqk pmyevqwkvv eeingnnyvy idptqlpydh kwefprnrls fgktlgagaf

601 gkvveatayg liksdaamtv avkmlkpsah Iterealmse Ikvlsylgnh mnivnllgac

661 tiggptlvit eyccygdlln flrrkrdsfi cskqedhaea alyknllhsk esscsdstne

721 ymdmkpgvsy vvptkadkrr svrigsyier dvtpaimedd elaldledll sfsyqvakgm

781 aflaskncih rdlaarnill thgritkicd fglardiknd snyvvkgnar Ipvkwmapes

841 ifncvytfes dvwsygiflw elfslgsspy pgmpvdskfy kmikegfrml spehapaemy

901 dimktcwdad plkrptfkqi vqliekqise stnhiysnla ncspnrqkpv vdhsvrinsv

961 gstasssqpl Ivhddv

Mast/stem cell growth acor receptor KIT, isoform 2 precursor NP_001087241.1 (SEQ ID NO: 277)

1 mrgargawdf Icvlllllrv qtgssqpsvs pgepsppsih pgksdlivrv gdeirllctd

61 pgfvkwtfei Idetnenkqn ewitekaeat ntgkytctnk hglsnsiyvf vrdpaklflv

121 drslygkedn dtlvrcpltd pevtnyslkg cqgkplpkdl rfipdpkagi miksvkrayh

181 rlclhcsvdq egksvlsekf ilkvrpafka vpvvsvskas yllregeeft vtctikdvss

241 svystwkren sqtklqekyn swhhgdfnye rqatltissa rvndsgvfmc yanntfgsan

301 vtttlevvdk gfinifpmin ttvfvndgen vdliveyeaf pkpehqqwiy mnrtftdkwe

361 dypksenesn iryvselhlt rlkgteggty tflvsnsdvn aaiafnvyvn tkpeiltydr

421 Ivngmlqcva agfpeptidw yfcpgteqrc sasvlpvdvq tlnssgppfg klvvqssids

481 safkhngtve ckayndvgkt sayfnfafke qihphtlftp lligfvivag mmciivmilt 541 ykylqkpmye vqwkvveein gnnyvyidpt qlpydhkwef prnrlsfgkt Igagafgkvv

601 eataygliks daamtvavkm Ikpsahlter ealmselkvl sylgnhmniv nllgactigg

661 ptlviteycc ygdllnflrr krdsficskq edhaeaalyk nllhskessc sdstneymdm

721 kpgvsyvvpt kadkrrsvri gsyierdvtp aimeddelal dledllsfsy qvakgmafla

781 skncihrdla arnillthgr itkicdfgla rdikndsnyv vkgnarlpvk wmapesifnc

841 vytfesdvws ygiflwelfs Igsspypgmp vdskfykmik egfrmlspeh apaemydimk

901 tcwdadplkr ptfkqivqli ekqisestnh iysnlancsp nrqkpvvdhs vrinsvgsta

961 sssqpllvhd dv

Plasma kallikrein isoform 1 preprotein NP_001639.1 (SEQ ID NO: 278)

1 mwvpvvfltl svtwigaapl ilsrivggwe cekhsqpwqv Ivasrgravc ggvlvhpqwv

61 Itaahcirnk svillgrhsl fhpedtgqvf qvshsfphpl ydmsllknrf Irpgddsshd

121 Imllrlsepa eltdavkvmd Iptqepalgt tcyasgwgsi epeefltpkk Iqcvdlhvis

181 ndvcaqvhpq kvtkfmlcag rwtggkstcs gdsggplvcn gvlqgitswg sepcalperp

241 slytkvvhyr kwikdtivan p

Plasma kallikrein isoform 3 preprotein NP_001025218.1 (SEQ ID NO: 279)

1 mwvpvvfltl svtwigaapl ilsrivggwe cekhsqpwqv Ivasrgravc ggvlvhpqwv

61 Itaahcirnk svillgrhsl fhpedtgqvf qvshsfphpl ydmsllknrf Irpgddsshd

121 Imllrlsepa eltdavkvmd Iptqepalgt tcyasgwgsi epeefltpkk Iqcvdlhvis

181 ndvcaqvhpq kvtkfmlcag rwtggkstcs wviliteltm palpmvlhgs Ivpwrggv

Plasma kallikrein isoform 4 preprotein NP_001025219.1 (SEQ ID NO: 280)

1 mwvpvvfltl svtwigaapl ilsrivggwe cekhsqpwqv Ivasrgravc ggvlvhpqwv

61 Itaahcirkp gddsshdlml Irlsepaelt davkvmdlpt qepalgttcy asgwgsiepe

121 efltpkklqc vdlhvisndv caqvhpqkvt kfmlcagrwt ggkstcsgds ggplvcngvl

181 qgitswgsep calperpsly tkvvhyrkwi kdtivanp

Tyrosine-protein kinase LCK, isoform a NP_001036236.1, NP_005347.3 (SEQ ID NO: 281)

1 mgcgcsshpe ddwmenidvc enchypivpl dgkgtllirn gsevrdplvt yegsnppasp

61 Iqdnlvialh syepshdgdl gfekgeqlri leqsgewwka qslttgqegf ipfnfvakan

121 slepepwffk nlsrkdaerq llapgnthgs fliresesta gsfslsvrdf dqnqgevvkh

181 ykirnldngg fyispritfp glhelvrhyt nasdglctrl srpcqtqkpq kpwwedewev

241 pretlklver Igagqfgevw mgyynghtkv avkslkqgsm spdaflaean Imkqlqhqrl

301 vrlyavvtqe piyiiteyme ngslvdflkt psgikltink lldmaaqiae gmafieerny

361 ihrdlraani Ivsdtlscki adfglarlie dneytarega kfpikwtape ainygtftik

421 sdvwsfgill teivthgrip ypgmtnpevi qnlergyrmv rpdncpeely qlmrlcwker

481 pedrptfdyl rsvledffta tegqyqpqp

Tyrosine-protein kinase LCK, isoform b NP_001317397.1 (SEQ ID NO: 282)

241 qdlvqekyle yrqvpdsdpa ryeflwgpra laetsyvkvl eyvikvsarv rfffpslrea 301 alreeeegv

Melanoma-associated antigen 10 NP_001011543.2_J NP_001238757.1, NP_066386.2 (SEQ ID NO: 286)

1 mprapkrqrc mpeedlqsqs etqglegaqa plaveedass ststsssfps sfpsssssss

61 sscyplipst peevsaddet pnppqsaqia csspsvvasl pldqsdegss sqkeespstl

121 qvlpdseslp rseidekvtd Ivqfllfkyq mkepitkaei lesvirnyed hfpllfseas

181 ecmllvfgid vkevdptghs fvlvtslglt ydgmlsdvqs mpktgilili Isiifiegyc

241 tpeeviweal nmmglydgme hliygeprkl Itqdwvqeny leyrqvpgsd paryeflwgp

301 rahaeirkms llkflakvng sdprsfplwy eealkdeeer aqdriattdd ttamasasss

361 atgsfsype

Melanoma-associated antigen 12 NP-001159858.1, NP_001159859.1, NP_005358.2 (SEQ ID NO: 287)

1 mpleqrsqhc kpeegleaqg ealglvgaqa pateeqetas ssstlvevtl revpaaesps

61 pphspqgast Ipttinytlw sqsdegssne eqegpstfpd letsfqvals rkmaelvhfl

121 llkyrarepf tkaemlgsvi rnfqdffpvi fskaseylql vfgievvevv righlyilvt

181 clglsydgll gdnqivpktg lliivlaiia kegdcapeek iweelsvlea sdgredsvfa

241 hprklltqdl vqenyleyrq vpgsdpacye flwgpralve tsyvkvlhhl Ikisggphis

301 ypplhewafr egee

Melanoma-associated antigen 2 NP_001269430.1, NP_001269431.1_J NP_001269433.1_J NP_001269434.1 , NP_005352.1_J NP_786884.1_J NP_786885.1 (SEQ ID NO: 288)

1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqqtas ssstlvevtl gevpaadsps

61 pphspqgass fsttinytlw rqsdegssnq eeegprmfpd lesefqaais rkmvelvhfl

121 llkyrarepv tkaemlesvl rncqdffpvi fskaseylql vfgievvevv pishlyilvt

181 clglsydgll gdnqvmpktg lliivlaiia iegdcapeek iweelsmlev fegredsvfa

241 hprkllmqdl vqenyleyrq vpgsdpacye flwgpralie tsyvkvlhht Ikiggephis

301 ypplheralr egee

MAGE family member A3 NP_005353.1 (SEQ ID NO: 289)

1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqeaas ssstlvevtl gevpaaespd

61 ppqspqgass Ipttmnyplw sqsyedssnq eeegpstfpd lesefqaais rkvaelvhfl

121 llkyrarepv tkaemlgsvv gnwqyffpvi fskassslql vfgielmevd pighlyifat

181 clglsydgll gdnqimpkag lliivlaiia regdcapeek iweelsvlev fegredsilg

241 dpkklltqhf vqenyleyrq vpgsdpacye flwgpralve tsyvkvlhhm vkisggphis

301 ypplhewvlr egee

Melanoma-associated antigen 4 NP_001011548.1, NP_001011549.1_J NP-OOlOllSSO.l, NP_002353.3 (SEQ ID NO: 290)

1 msseqksqhc kpeegveaqe ealglvgaqa ptteeqeaav ssssplvpgt leevpaaesa

61 gppqspqgas alpttisftc wrqpnegsss qeeegpstsp daeslfreal snkvdelahf

121 llrkyrakel vtkaemlerv iknykrcfpv ifgkaseslk mifgidvkev dpasntytlv

181 tclglsydgl Ignnqifpkt glliivlgti amegdsasee eiweelgvmg vydgrehtvy

241 geprklltqd wvqenyleyr qvpgsnpary eflwgprala etsyvkvleh vvrvnarvri

301 aypslreaal leeeegv

Melanoma-associated antigen 6 NP_005354.1_J NP_787064.1 (SEQ ID NO: 291)

1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqeaas ssstlvevtl gevpaaespd

61 ppqspqgass Ipttmnyplw sqsyedssnq eeegpstfpd lesefqaais rkvaklvhfl

121 llkyrarepv tkaemlgsvv gnwqyffpvi fskasdslql vfgielmevd pighvyifat

181 clglsydgll gdnqimpktg fliiilaiia kegdcapeek iweelsvlev fegredsifg

241 dpkklltqyf vqenyleyrq vpgsdpacye flwgpralie tsyvkvlhhm vkisggpris

301 ypllhewalr egee

Melanoma-associated antigen 9 NP_005356.1 (SEQ ID NO: 292)

1 msleqrsphc kpdedleaqg edlglmgaqe ptgeeeetts ssdskeeevs aagsssppqs

61 pqggasssis vyytlwsqfd egsssqeeee psssvdpaql efmfqealkl kvaelvhfll

121 hkyrvkepvt kaemlesvik nykryfpvif gkasefmqvi fgtdvkevdp aghsyilvta

181 Iglscdsmlg dghsmpkaal liivlgvilt kdncapeevi wealsvmgvy vgkehmfyge

241 prklltqdwv qenyleyrqv pgsdpahyef Iwgskahaet syekvinylv mlnarepicy

301 pslyeevlge eqegv

Melanoma-associated antigen 02 NP_057333.1 (SEQ ID NO: 293)

1 mppvpgvpfr nvdndsptsv eledwvdaqh ptdeeeeeas sasstlylvf spssfstsss

61 lilggpeeee vpsgvipnlt esipssppqg ppqgpsqspl ssccssfsws sfseesssqk

121 gedtgtcqgl pdsessftyt Idekvaelve flllkyeaee pvteaemlmi vikykdyfpv

181 ilkrarefme llfglaliev gpdhfcvfan tvgltdegsd degmpensll iiilsvifik 241 gncaseeviw evlnavgvya grehfvygep relltkvwvq ghyleyrevp hssppyyefl 301 wgprahsesi kkkvleflak Inntvpssfp swykdalkdv eervqatidt addatvmase 361 slsvmssnvs fse

Melanoma-associated antigen DI, isoform a NP_001005333.1 (SEQ ID NO: 294)

1 maqkmdcgag llgfqnpdac ravchplpqp pastlplsaf ptlcdppysq Irdppavlsc

61 yctplgaspa paeasvedsa llmqtlmeai qiseapptnq ataaaspqss qpptanemad

121 iqvsaaaarp ksafkvqnat tkgpngvydf sqahnakdvp ntqpkaafks qnatpkgpna

181 aydfsqaatt gelaanksem afkaqnattk vgpnatynfs qslnandlan srpktpfkaw

241 ndttkaptad tqtqnvnqak matsqadiet dpgisepdga taqtsadgsq aqnlesrtii

301 rgkrtrkinn Inveenssgd qrraplaagt wrsapvpvtt qnppgappnv Iwqtplawqn

361 psgwqnqtar qtpparqspp arqtppawqn pvawqnpviw pnpviwqnpv iwpnpivwpg

421 pvvwpnplaw qnppgwqtpp gwqtppgwqg ppdwqgppdw plppdwplpp dwplptdwpl

481 ppdwipadwp ippdwqnlrp spnlrpspns rasqnpgaaq prdvallqer anklvkylml

541 kdytkvpikr semlrdiire ytdvypeiie racfvlekkf giqlkeidke ehlyilistp

601 eslagilgtt kdtpklglll vilgvifmng nraseavlwe alrkmglrpg vrhpllgdlr

661 klltyefvkq kyldyrrvpn snppeyeflw glrsyhetsk mkvlrfiaev qkrdprdwta

721 qfmeaadeal daldaaaaea earaeartrm gigdeavsgp wswddiefel Itwdeegdfg

781 dpwsripftf waryhqnars rfpqtfagpi igpggtasan faanfgaigf fwve

Melanoma-associated antigen DI, isoform b NP_001005332.1, NP_008917.3 (SEQ ID NO:

295)

1 maqkmdcgag llgfqaeasv edsallmqtl meaiqiseap ptnqataaas pqssqpptan

61 emadiqvsaa aarpksafkv qnattkgpng vydfsqahna kdvpntqpka afksqnatpk

121 gpnaaydfsq aattgelaan ksemafkaqn attkvgpnat ynfsqslnan dlansrpktp

181 fkawndttka ptadtqtqnv nqakmatsqa dietdpgise pdgataqtsa dgsqaqnles

241 rtiirgkrtr kinnlnveen ssgdqrrapl aagtwrsapv pvttqnppga ppnvlwqtpl

301 awqnpsgwqn qtarqtppar qspparqtpp awqnpvawqn pviwpnpviw qnpviwpnpi

361 vwpgpvvwpn plawqnppgw qtppgwqtpp gwqgppdwqg ppdwplppdw plppdwplpt

421 dwplppdwip adwpippdwq nlrpspnlrp spnsrasqnp gaaqprdval Iqeranklvk

481 ylmlkdytkv pikrsemlrd iireytdvyp eiieracfvl ekkfgiqlke idkeehlyil

541 istpeslagi Igttkdtpkl glllvilgvi fmngnrasea vlwealrkmg Irpgvrhpll

601 gdlrklltye fvkqkyldyr rvpnsnppey eflwglrsyh etskmkvlrf iaevqkrdpr

661 dwtaqfmeaa dealdaldaa aaeaearaea rtrmgigdea vsgpwswddi efelltwdee

721 gdfgdpwsri pftfwaryhq narsrfpqtf agpiigpggt asanfaanfg aigffwve

Mitogen-activated protein kinase kinase kinase 5 NP_005914.1 (SEQ ID NO:

296)

1 msteadegit fsvppfapsg fctipeggic rrggaaavge geehqlpppp pgsfwnvesa

61 aapgigcpaa tssssatrgr gssvgggsrr ttvayvinea sqgqlvvaes ealqslreac

121 etvgatletl hfgkldfget tvldrfynad iavvemsdaf rqpslfyhlg vresfsmann

181 iilycdtnsd slqslkeiic qkntmctgny tfvpymitph nkvyccdssf mkgltelmqp

241 nfelllgpic Iplvdrfiql Ikvaqasssq yfresilndi rkarnlytgk elaaelarir

301 qrvdnievlt adivinllls yrdiqdydsi vklvetlekl ptfdlashhh vkfhyafaln

361 rrnlpgdrak aldimipmvq segqvasdmy clvgriykdm fldsnftdte srdhgaswfk

421 kafeseptlq sginyavlll aaghqfessf elrkvgvkls sllgkkgnle klqsywevgf

481 flgasvland hmrviqasek Ifklktpawy Iksivetili ykhfvkltte qpvakqelvd

541 fwmdflveat ktdvtvvrfp vlileptkiy qpsylsinne veektisiwh vlpddkkgih

601 ewnfsassvr gvsiskfeer ccflyvlhns ddfqiyfcte Ihckkffemv ntiteekgrs

661 teegdcesdl leydyeyden gdrvvlgkgt ygivyagrdl snqvriaike iperdsrysq

721 plheeialhk hlkhknivqy Igsfsengfi kifmeqvpgg slsallrskw gplkdneqti

781 gfytkqileg Ikylhdnqiv hrdikgdnvl intysgvlki sdfgtskrla ginpctetft

841 gtlqymapei idkgprgygk aadiwslgct iiematgkpp fyelgepqaa mfkvgmfkvh

901 peipesmsae akafilkcfe pdpdkracan dllvdeflkv sskkkktqpk Isalsagsne

961 ylrsislpvp vlvedtssss eygsvspdte Ikvdpfsfkt rakscgerdv kgirtlflgi

1021 pdenfedhsa ppspeekdsg ffmlrkdser ratlhrilte dqdkivrnlm eslaqgaeep

1081 klkwehittl iaslrefvrs tdrkiiattl sklkleldfd shgisqvqvv Ifgfqdavnk

1141 vlrnhnikph wmfaldsiir kavqtaitil vpelrphfsl asesdtadqe dldveddhee

1201 qpsnqtvrrp qaviedavat sgvstlsstv shdsqsahrs Invqlgrmki etnrlleelv

1261 rkekelqall hraieekdqe ikhlklksqp ieipelpvfh Inssgtnted seltdwlrvn

1321 gadedtisrf laedytlldv lyyvtrddlk clrlrggmlc tlwkaiidfr nkqt

Mitogen-activated protein kinase kinase kinase 9, isoform 1 NP_149132.2

(SEQ ID NO: 297)

1 mepsrallgc lasaaaaapp gedgagagae eeeeeeeeaa aavgpgelgc daplpywtav 61 feyeaagede Itlrlgdvve vlskdsqvsg degwwtgqln qrvgifpsny vtprsafssr

121 cqpggedpsc yppiqlleid faeltleeii giggfgkvyr afwigdevav kaarhdpded

181 isqtienvrq eaklfamlkh pniialrgvc Ikepnlclvm efarggplnr vlsgkrippd

241 ilvnwavqia rgmnylhdea ivpiihrdlk ssnililqkv engdlsnkil kitdfglare

301 whrttkmsaa gtyawmapev irasmfskgs dvwsygvllw elltgevpfr gidglavayg

361 vamnklalpi pstcpepfak Imedcwnpdp hsrpsftnil dqlttieesg ffempkdsfh

421 clqdnwkhei qemfdqlrak ekelrtweee Itraalqqkn qeellrrreq elaereidil

481 erelniiihq Icqekprvkk rkgkfrksrl klkdgnrisl psdfqhkftv qasptmdkrk

541 slinsrsspp asptiiprlr aiqltpgess ktwgrssvvp keegeeeekr apkkkgrtwg

601 pgtlgqkela sgdegspqrr ekanglstps esphfhlglk slvdgykqws ssapnlvkgp

661 rsspalpgft slmemallaa swvvpidiee dedsegpgsg esrlqhspsq sylcipfprg

721 edgdgpssdg iheeptpvns atstpqltpt nslkrggahh rrcevallgc gavlaatglg

781 fdlleagkcq llpleepepp areekkrreg Ifqrssrprr stsppsrklf kkeepmlllg

841 dpsasltlls Issisecnst rsllrsdsde ivvyempvsp veapplspct hnplvnvrve

901 rfkrdpnqsl tpthvtlttp sqpsshrrtp sdgalkpetl lasrspssng Ispspgagml

961 ktpspsrdpg efprlpdpnv vfpptprrwn tqqdstlerp ktleflprpr psanrqrldp

1021 wwfvspshar stspanssst etpsnldscf asssstveer pglpallpfq agplpptert

1081 lldldaegqs qdstvplcra elnthrpapy eiqqefws

Mitogen-activated protein kinase kinase kinase 9, isoform 2 NP_001271159.1 (SEQ ID NO: 298)

1 mepsrallgc lasaaaaapp gedgagagae eeeeeeeeaa aavgpgelgc daplpywtav

61 feyeaagede Itlrlgdvve vlskdsqvsg degwwtgqln qrvgifpsny vtprsafssr

121 cqpggedpsc yppiqlleid faeltleeii giggfgkvyr afwigdevav kaarhdpded

181 isqtienvrq eaklfamlkh pniialrgvc Ikepnlclvm efarggplnr vlsgkrippd

241 ilvnwavqia rgmnylhdea ivpiihrdlk ssnililqkv engdlsnkil kitdfglare

301 whrttkmsaa gtyawmapev irasmfskgs dvwsygvllw elltgevpfr gidglavayg

361 vamnklalpi pstcpepfak Imedcwnpdp hsrpsftnil dqlttieesg ffempkdsfh

421 clqdnwkhei qemfdqlrak ekelrtweee Itraalqqkn qeellrrreq elaereidil

481 erelniiihq Icqekprvkk rkgkfrksrl klkdgnrisl psdfqhkftv qasptmdkrk

541 slinsrsspp asptiiprlr aiqltpgess ktwgrssvvp keegeeeekr apkkkgrtwg

601 pgtlgqkela sgdegspqrr ekanglstps esphfhlglk slvdgykqws ssapnlvkgp

661 rsspalpgft slmemededs egpgsgesrl qhspsqsylc ipfprgedgd gpssdgihee

721 ptpvnsatst pqltptnslk rggahhrrce vallgcgavl aatglgfdll eagkcqllpl

781 eepepparee kkrreglfqr ssrprrstsp psrklfkkee pmlllgdpsa sltllslssi

841 secnstrsll rsdsdeivvy empvspveap plspcthnpl vnvrverfkr dpnqsltpth

901 vtlttpsqps shrrtpsdga Ikpetllasr spssnglsps pgagmlktps psrdpgefpr

961 Ipdpnvvfpp tprrwntqqd stlerpktle flprprpsan rqrldpwwfv spsharstsp

1021 anssstetps nldscfasss stveerpglp allpfqagpl pptertlldl daegqsqdst

1081 vplcraelnt hrpapyeiqq efws

Mitogen-activated protein kinase kinase kinase 9, isoform 3 NP_001271160.1 (SEQ ID NO: 299)

1 meltgleval vlilqkveng dlsnkilkit dfglarewhr ttkmsaagty awmapevira

61 smfskgsdvw sygvllwell tgevpfrgid glavaygvam nklalpipst cpepfaklme

121 dcwnpdphsr psftnildql ttieesgffe mpkdsfhclq dnwkheiqem fdqlrakeke

181 Irtweeeltr aalqqknqee llrrreqela ereidilere Iniiihqlcq ekprvkkrkg

241 kfrksrlklk dgnrislpsd fqhkftvqas ptmdkrksli nsrssppasp tiiprlraiq

301 cetvsqiswg qntqghlspa Isshrlvqac sihnfchlss tmciymhilt pgessktwgr

361 ssvvpkeege eeekrapkkk grtwgpgtlg qkelasgdeg Ikslvdgykq wsssapnlvk

421 gprsspalpg ftslmemall aaswvvpidi eededsegpg sgesrlqhsp sqsylcipfp

481 rgedgdgpss dgiheeptpv nsatstpqlt ptnslkrgga hhrrcevall gcgavlaatg

541 Igfdlleagk cqllpleepe ppareekkrr eglfqrssrp rrstsppsrk Ifkkeepmll

601 Igdpsasltl Islssisecn strsllrsds deivvyempv spveapplsp cthnplvnvr

661 verfkrdpnq sltpthvtlt tpsqpsshrr tpsdgalkpe tllasrspss nglspspgag

721 mlktpspsrd pgefprlpdp nvvfpptprr wntqqdstle rpktleflpr prpsanrqrl

781 dpwwfvspsh arstspanss stetpsnlds cfasssstve erpglpallp fqagplppte

841 rtlldldaeg qsqdstvplc raelnthrpa pyeiqqefws

Mitogen-activated protein kinase kinase kinase 9, isoform 4 NP_001271161.1 (SEQ ID NO: 300)

1 msaagtyawm apevirasmf skgsdvwsyg vllwelltge vpfrgidgla vaygvamnkl

61 alpipstcpe pfaklmedcw npdphsrpsf tnildqltti eesgffempk dsfhclqdnw

121 kheiqemfdq Irakekelrt weeeltraal qqknqeellr rreqelaere idilerelni 181 iihqlcqekp rvkkrkgkfr ksrlklkdgn rislpsdfqh kftvqasptm dkrkslinsr

241 ssppasptii prlraiqcet vsqiswgqnt qghlspalss hrlvqacsih nfchlsstmc

301 iymhiltpge ssktwgrssv vpkeegeeee krapkkkgrt wgpgtlgqke lasgdeglks

361 Ivdgykqwss sapnlvkgpr sspalpgfts Imemallaas wvvpidieed edsegpgsge

421 srlqhspsqs ylcipfprge dgdgpssdgi heeptpvnsa tstpqltptn slkrggahhr

481 rcevallgcg avlaatglgf dlleagkcql Ipleepeppa reekkrregl fqrssrprrs

541 tsppsrklfk keepmlllgd psasltllsl ssisecnstr sllrsdsdei vvyempvspv

601 eapplspcth nplvnvrver fkrdpnqslt pthvtlttps qpsshrrtps dgalkpetll

661 asrspssngl spspgagmlk tpspsrdpge fprlpdpnvv fpptprrwnt qqdstlerpk

721 tleflprprp sanrqrldpw wfvspshars tspanssste tpsnldscfa sssstveerp

781 glpallpfqa gplpptertl Idldaegqsq dstvplcrae Inthrpapye iqqefws

Mitogen-activated protin kinase 1 NP_002736.3, NP_620407.1 (SEQ ID NO: 301)

1 maaaaaagag pemvrgqvfd vgprytnlsy igegaygmvc saydnvnkvr vaikkispfe

61 hqtycqrtlr eikillrfrh eniigindii raptieqmkd vyivqdlmet dlykllktqh

121 Isndhicyfl yqilrglkyi hsanvlhrdl kpsnlllntt cdlkicdfgl arvadpdhdh

181 tgflteyvat rwyrapeiml nskgytksid iwsvgcilae mlsnrpifpg khyldqlnhi

241 Igilgspsqe dlnciinlka rnyllslphk nkvpwnrlfp nadskaldll dkmltfnphk

301 rieveqalah pyleqyydps depiaeapfk fdmelddlpk eklkelifee tarfqpgyrs

Melan-A NP_005502.1 (SEQ ID NO: 302)

1 mpredahfiy gypkkghghs yttaeeaagi giltvilgvl lligcwycrr rngyralmdk

61 slhvgtqcal trrcpqegfd hrdskvslqe kncepvvpna ppayeklsae qspppysp

Melanotransferrin, isoform 1 preprotein NP_005920.2 (SEQ ID NO: 303)

1 mrgpsgalwl llalrtvlgg mevrwcatsd peqhkcgnms eafreagiqp sllcvrgtsa

61 dhcvqliaaq eadaitldgg aiyeagkehg Ikpvvgevyd qevgtsyyav avvrrsshvt

121 idtlkgvksc htginrtvgw nvpvgylves grlsvmgcdv Ikavsdyfgg scvpgagets

181 yseslcrlcr gdssgegvcd kspleryydy sgafrclaeg agdvafvkhs tvlentdgkt

241 Ipswgqalls qdfellcrdg sradvtewrq chlarvpaha vvvradtdgg lifrllnegq

301 rlfshegssf qmfsseaygq kdllfkdsts elvpiatqty eawlgheylh amkgllcdpn

361 rlppylrwcv Istpeiqkcg dmavafrrqr Ikpeiqcvsa kspqhcmeri qaeqvdavtl

421 sgediytagk tyglvpaage hyapedssns yyvvavvrrd sshaftldel rgkrschagf

481 gspagwdvpv galiqrgfir pkdcdvltav seffnascvp vnnpknypss Icalcvgdeq

541 grnkcvgnsq eryygyrgaf rclvenagdv afvrhttvfd ntnghnsepw aaelrsedye

601 llcpngarae vsqfaacnla qipphavmvr pdtniftvyg lldkaqdlfg ddhnkngfkm

661 fdssnyhgqd llfkdatvra vpvgekttyr gwlgldyvaa legmssqqcs gaaapapgap

721 llplllpala arllppal

Melanotransferrin, isoform 2 precursor NP_201573.1 (SEQ ID NO: 304)

1 mrgpsgalwl llalrtvlgg mevrwcatsd peqhkcgnms eafreagiqp sllcvrgtsa

61 dhcvqliaaq eadaitldgg aiyeagkehg Ikpvvgevyd qevgtsyyav avvrrsshvt

121 idtlkgvksc htginrtvgw nvpvgylves grlsvmgcdv Ikavsdyfgg scvpgagets

181 yseslcrlcr gdssgegvcd kspleryydy sgafrclaeg agdvafvkhs tvlentdesp

241 srrqtwtrse eeegecpahe earrtmrssa gqawkwapvh rpqdesdkge fgkraksrdm

301 1g

Baculoviral IAP repeat containing 7, isoform alpha NP_647478.1 (SEQ ID NO: 305)

1 mgpkdsakcl hrgpqpshwa agdgptqerc gprslgspvl gldtcrawdh vdgqilgqlr

61 plteeeeeeg agatlsrgpa fpgmgseelr lasfydwplt aevppellaa agffhtghqd

121 kvrcffcygg Iqswkrgddp wtehakwfps cqfllrskgr dfvhsvqeth sqllgswdpw

181 eepedaapva psvpasgype Iptprrevqs esaqepggvs paeaqrawwv leppgardve

241 aqlrrlqeer tckvcldrav sivfvpcghl vcaecapglq Icpicrapvr srvrtfls

Baculoviral IAP repeat containing 7, isoform beta NP_071444.1 (SEQ ID NO: 306)

1 mgpkdsakcl hrgpqpshwa agdgptqerc gprslgspvl gldtcrawdh vdgqilgqlr

61 plteeeeeeg agatlsrgpa fpgmgseelr lasfydwplt aevppellaa agffhtghqd

121 kvrcffcygg Iqswkrgddp wtehakwfps cqfllrskgr dfvhsvqeth sqllgswdpw

181 eepedaapva psvpasgype Iptprrevqs esaqepgard veaqlrrlqe ertckvcldr

241 avsivfvpcg hlvcaecapg Iqlcpicrap vrsrvrtfls

Neutrophil collagenase, isoform 1 preprotein NP_002415.1 (SEQ ID NO: 307)

1 mfslktlpfl lllhvqiska fpvsskeknt ktvqdylekf yqlpsnqyqs trkngtnviv

61 eklkemqrff glnvtgkpne etldmmkkpr cgvpdsggfm Itpgnpkwer tnltyrirny

121 tpqlseaeve raikdafelw svaspliftr isqgeadini afyqrdhgdn spfdgpngil

181 ahafqpgqgi ggdahfdaee twtntsanyn Iflvaahefg hslglahssd pgalmypnya

241 fretsnyslp qddidgiqai yglssnpiqp tgpstpkpcd psltfdaitt Irgeilffkd 301 ryfwrrhpql qrvemnfisl fwpslptgiq aayedfdrdl iflfkgnqyw alsgydilqg 361 ypkdisnygf pssvqaidaa vfyrsktyff vndqfwrydn qrqfmepgyp ksisgafpgi 421 eskvdavfqq ehffhvfsgp ryyafdliaq rvtrvargnk wlncryg

Neutrophil collagenase, isoform 2 NP_001291370.1, NP_001291371.1 (SEQ ID NO: 308)

1 mqqipqeksi ndylekfyql psnqyqstrk ngtnvivekl kemqrffgln vtgkpneetl

61 dmmkkprcgv pdsggfmltp gnpkwertnl tyrirnytpq Iseaeverai kdafelwsva

121 spliftrisq geadiniafy qrdhgdnspf dgpngilaha fqpgqgiggd ahfdaeetwt

181 ntsanynlfl vaahefghsl glahssdpga Imypnyafre tsnyslpqdd idgiqaiygl

241 ssnpiqptgp stpkpcdpsl tfdaittlrg eilffkdryf wrrhpqlqrv emnfislfwp

301 slptgiqaay edfdrdlifl fkgnqywals gydilqgypk disnygfpss vqaidaavfy

361 rsktyffvnd qfwrydnqrq fmepgypksi sgafpgiesk vdavfqqehf fhvfsgpryy

421 afdliaqrvt rvargnkwln cryg

Mesothelin, isoform 1 preprotein NP_001170826.1, NP_005814.2 (SEQ ID NO: 309)

1 malptarpll gscgtpalgs llfllfslgw vqpsrtlage tgqeaapldg vlanppniss

61 Isprqllgfp caevsglste rvrelavala qknvklsteq Irclahrlse ppedldalpl

121 dlllflnpda fsgpqactrf fsritkanvd llprgaperq rllpaalacw gvrgsllsea

181 dvralgglac dlpgrfvaes aevllprlvs cpgpldqdqq eaaraalqgg gppygppstw

241 svstmdalrg llpvlgqpii rsipqgivaa wrqrssrdps wrqpertilr prfrrevekt

301 acpsgkkare ideslifykk weleacvdaa llatqmdrvn aipftyeqld vlkhkldely

361 pqgypesviq hlgylflkms pedirkwnvt sletlkalle vnkghemspq vatlidrfvk

421 grgqldkdtl dtltafypgy Icslspeels svppssiwav rpqdldtcdp rqldvlypka

481 rlafqnmngs eyfvkiqsfl ggaptedlka Isqqnvsmdl atfmklrtda vlpltvaevq

541 kllgphvegl kaeerhrpvr dwilrqrqdd Idtlglglqg gipngylvld Ismqealsgt

601 pcllgpgpvl tvlalllast la

Mesothelin, isoform 2 preprotein NP_037536.2 (SEQ ID NO: 310)

1 malptarpll gscgtpalgs llfllfslgw vqpsrtlage tgqeaapldg vlanppniss

61 Isprqllgfp caevsglste rvrelavala qknvklsteq Irclahrlse ppedldalpl

121 dlllflnpda fsgpqactrf fsritkanvd llprgaperq rllpaalacw gvrgsllsea

181 dvralgglac dlpgrfvaes aevllprlvs cpgpldqdqq eaaraalqgg gppygppstw

241 svstmdalrg llpvlgqpii rsipqgivaa wrqrssrdps wrqpertilr prfrrevekt

301 acpsgkkare ideslifykk weleacvdaa llatqmdrvn aipftyeqld vlkhkldely

361 pqgypesviq hlgylflkms pedirkwnvt sletlkalle vnkghemspq aprrplpqva

421 tlidrfvkgr gqldkdtldt Itafypgylc slspeelssv ppssiwavrp qdldtcdprq

481 Idvlypkarl afqnmngsey fvkiqsflgg aptedlkals qqnvsmdlat fmklrtdavl

541 pltvaevqkl Igphveglka eerhrpvrdw ilrqrqddld tlglglqggi pngylvldls

601 mqealsgtpc llgpgpvltv lalllastla

Mucin-1, isoform 1 precursor NP_002447.4 (SEQ ID NO: 311)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knalstgvsf

61 fflsfhisnl qfnssledps tdyyqelqrd isemflqiyk qggflglsni kfrpgsvvvq

121 Itlafregti nvhdvetqfn qykteaasry nltisdvsvs dvpfpfsaqs gagvpgwgia

181 llvlvcvlva laivyliala vcqcrrknyg qldifpardt yhpmseypty hthgryvpps

241 stdrspyekv sagnggssls ytnpavaats anl

Mucin-1, isoform 2 precursor NP_001018016.1 (SEQ ID NO: 312)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nafnssledp stdyyqelqr disemflqiy kqggflglsn ikfrpgsvvv qltlafregt

121 invhdvetqf nqykteaasr ynltisdvsv sdvpfpfsaq sgagvpgwgi allvlvcvlv

181 alaivylial avcqcrrkny gqldifpard tyhpmseypt yhthgryvpp sstdrspyek

241 vsagnggssl sytnpavaat sanl

Mucin-1, isoform 3 precursor NP_001018017.1 (SEQ ID NO: 313)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knafnssled

61 pstdyyqelq rdisemflqi ykqggflgls nikfrpgsvv vqltlafreg tinvhdvetq

121 fnqykteaas rynltisdvs vsdvpfpfsa qsgagvpgwg iallvlvcvl valaivylia

181 lavcqcrrkn ygqldifpar dtyhpmseyp tyhthgryvp psstdrspye kvsagnggss

241 Isytnpavaa tsanl

Mucin-1, isoform 5 precursor NP_001037855.1 (SEQ ID NO: 314)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knaipapttt

61 kscretflkc fcrfinkgvf waspilssvs dvpfpfsaqs gagvpgwgia llvlvcvlva

121 laivyliala vcqcrrknyg qldifpardt yhpmseypty hthgryvpps stdrspyekv

181 sagnggssls ytnpavaats anl

Mucin-1, isoform 6 precursor NP_001037856.1 (SEQ ID NO: 315)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knafnssled 61 pstdyyqelq rdisemavcq crrknygqld ifpardtyhp mseyptyhth gryvppsstd

121 rspyekvsag nggsslsytn pavaatsanl

Mucin-lj isoform 7 precursor NP_001037857.1 (SEQ ID NO: 316)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nafnssledp stdyyqelqr disemavcqc rrknygqldi fpardtyhpm seyptyhthg

121 ryvppsstdr spyekvsagn ggsslsytnp avaatsanl

Mucin-lj isoform 8 precursor NP_001037858.1 (SEQ ID NO: 317)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knaipapttt 61 kscretflkc fcrfinkgvf waspilssvw gwgarlghra agaglcsgca ghclshclgc 121 Isvppkelra aghlsspgyl psyervphlp hpwalcap

Mucin-lj isoform 9 precursor NP_001191214.1 (SEQ ID NO: 318)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knavsmtssv

61 Isshspgsgs sttqgqdvtl apatepasgs aatwgqdvts vpvtrpalgs ttppahdvts

121 apdnkpapgs tappahgvts apdtrpapgs tappahgvts apdnrpalgs tappvhnvts

181 asgsasgsas tlvhngtsar atttpaskst pfsipshhsd tpttlashst ktdassthhs

241 tvppltssnh stspqlstgv sffflsfhis nlqfnssled pstdyyqelq rdisemflqi

301 ykqggflgls nikfrpgsvv vqltlafreg tinvhdvetq fnqykteaas rynltisdvs

361 vsdvpfpfsa qsgagvpgwg iallvlvcvl valaivylia lavcqcrrkn ygqldifpar

421 dtyhpmseyp tyhthgryvp psstdrspye kvsagnggss Isytnpavaa tsanl

Mucin-lj isoform 10 precursor NP_001191215.1 (SEQ ID NO: 319)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 navsmtssvl sshspgsgss ttqgqdvtla patepasgsa atwgqdvtsv pvtrpalgst

121 tppahdvtsa pdnkpapgst appahgvtsa pdtrpapgst appahgvtsa pdnrpalgst

181 appvhnvtsa sgsasgsast Ivhngtsara tttpaskstp fsipshhsdt pttlashstk

241 tdassthhst vppltssnhs tspqlstgvs ffflsfhisn Iqfnssledp stdyyqelqr

301 disemflqiy kqggflglsn ikfrpgsvvv qltlafregt invhdvetqf nqykteaasr

361 ynltisdvsv sdvpfpfsaq sgagvpgwgi allvlvcvlv alaivylial avcqcrrkny

421 gqldifpard tyhpmseypt yhthgryvpp sstdrspyek vsagnggssl sytnpavaat

481 sanl

Mucin-lj isoform 11 precursor NP_001191216.1 (SEQ ID NO: 320)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nalstgvsff flsfhisnlq fnssledpst dyyqelqrdi semflqiykq ggflglsnik

121 frpgsvvvql tlafregtin vhdvetqfnq ykteaasryn Itisdvsvsd vpfpfsaqsg

181 agvpgwgial Ivlvcvlval aivylialav cqcrrknygq Idifpardty hpmseyptyh

241 thgryvppss tdrspyekvs agnggsslsy tnpavaatsa nl

Mucin-1, isoform 12 precursor NP_001191217.1 (SEQ ID NO: 321)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nafnssledp stdyyqelqr disemflqiy kqggflglsn ikfrpgsvvv qltlafregt

121 invhdvetqf nqykteaasr ynltisdvsv wgwgarlghr aagaglcsgc aghclshclg

181 clsvppkelr aaghlsspgy Ipsyervphl phpwalcap

Mucin-1, isoform 13 precursor NP_001191218.1 (SEQ ID NO: 322)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 naiykqggfl glsnikfrpg svvvqltlaf regtinvhdv etqfnqykte aasrynltis

121 dvsvsdvpfp fsaqsgagvp gwgiallvlv cvlvalaivy lialavcqcr rknygqldif

181 pardtyhpms eyptyhthgr yvppsstdrs pyekvsagng gsslsytnpa vaatsanl

Mucin-1, isoform 14 precursor NP_001191219.1 (SEQ ID NO: 323)

1 mtpgtqspff llllltvltg geketsatqr ssvpsstekn aiykqggflg Isnikfrpgs

61 vvvqltlafr egtinvhdve tqfnqyktea asrynltisd vsvsdvpfpf saqsgagvpg

121 wgiallvlvc vlvalaivyl ialavcqcrr knygqldifp ardtyhpmse yptyhthgry

181 vppsstdrsp yekvsagngg sslsytnpav aatsanl

Mucin-1, isoform 15 precursor NP_001191220.1 (SEQ ID NO: 324)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek 61 naflqiykqg gflglsnikf rpgsvvvqlt lafregtinv hdvetqfnqy kteaasrynl 121 tisdvsvsdv pfpfsaqsga gvpgwgiall vlvcvlvala ivylialavc qcrrknygql 181 difpardtyh pmseyptyht hgryvppsst drspyekvsa gnggsslsyt npavaatsan 241 1

Mucin-1, isoform 16 precursor NP_001191221.1 (SEQ ID NO: 325)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek 61 naipaptttk scretflkwp gsvvvqltla fregtinvhd vetqfnqykt eaasrynlti 121 sdvsvsdvpf pfsaqsgagv pgwgiallvl vcvlvalaiv ylialavcqc rrknygqldi 181 fpardtyhpm seyptyhthg ryvppsstdr spyekvsagn ggsslsytnp avaatsanl Mucin-1, isoform 17 precursor NP_001191222.1 (SEQ ID NO: 326)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knalstgvsf

61 fflsfhisnl qfnssledps tdyyqelqrd isemflqiyk qggflglsni kfrpgsvvvq

121 Itlafregti nvhdvetqfn qykteaasry nltisdvsgc Isvppkelra aghlsspgyl

181 psyervphlp hpwalcap

Mucin-1, isoform 18 precursor NP_001191223.1 (SEQ ID NO: 327)

1 mtpgtqspff llllltvltv vtgsghasst pggeketsat qrssvpsste knaipapttt 61 kscretflkw pgsvvvqltl afregtinvh dvetqfnqyk teaasrynlt isdvsvsdvp 121 fpfsaqsgag vpgwgiallv Ivcvlvalai vylialavcq crrknygqld ifpardtyhp 181 mseyptyhth gryvppsstd rspyekvsag nggsslsytn pavaatsanl

Mucin-1, isoform 19 precursor NP_001191224.1 (SEQ ID NO: 328)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nafnssledp stdyyqelqr disemsgagv pgwgiallvl vcvlvalaiv ylialavcqc

121 rrknygqldi fpardtyhpm seyptyhthg ryvppsstdr spyekvsagn ggsslsytnp

181 avaatsanl

Mucin-1, isoform 20 precursor NP_001191225.1 (SEQ ID NO: 329)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 naipaptttk scretflkcf crfinkgvfw aspilssvsd vpfpfsaqsg agvpgwgial

121 Ivlvcvlval aivylialav cqcrrknygq Idifpardty hpmseyptyh thgryvppss

181 tdrspyekvs agnggsslsy tnpavaatsa nl

Mucin-1, isoform 21 precursor NP_001191226.1 (SEQ ID NO: 330)

1 mtpgtqspff llllltvlta ttapkpatvv tgsghasstp ggeketsatq rssvpsstek

61 nalstgvsff flsfhisnlq fnssledpst dyyqelqrdi semavcqcrr knygqldifp

121 ardtyhpmse yptyhthgry vppsstdrsp yekvsagngg sslsytnpav aatsanl

N-myc proto-oncogene protein, isoform 1 NP_001280157.1, NP_005369.2 (SEQ ID NO: 331)

1 mpscststmp gmicknpdle fdslqpcfyp deddfyfggp dstppgediw kkfellptpp

61 Ispsrgfaeh sseppswvte mllenelwgs paeedafglg glggltpnpv ilqdcmwsgf

121 sareklerav seklqhgrgp ptagstaqsp gagaaspagr ghggaagagr agaalpaela

181 hpaaecvdpa vvfpfpvnkr epapvpaapa sapaagpava sgagiaapag apgvapprpg

241 grqtsggdhk alstsgedtl sdsddeddee edeeeeidvv tvekrrsssn tkavttftit

301 vrpknaalgp graqsselil krclpihqqh nyaapspyve sedappqkki kseasprplk

361 svippkaksl sprnsdseds errrnhnile rqrrndlrss fltlrdhvpe Ivknekaakv

421 vilkkateyv hslqaeehql llekeklqar qqqllkkieh arte

N-myc proto-oncogene protein, isoform 2 NP_001280160.1 (SEQ ID NO: 332)

1 mrgapgncvg aeqalarrkr aqtvairghp rppgppgdtr aesppdplqs agddeddeee

61 deeeeidvvt vekrrsssnt kavttftitv rpknaalgpg raqsselilk rclpihqqhn

121 yaapspyves edappqkkik seasprplks vippkaksls prnsdsedse rrrnhniler

181 qrrndlrssf Itlrdhvpel vknekaakvv ilkkateyvh slqaeehqll lekeklqarq

241 qqllkkieha rtc

N-myc proto-oncogene protein, isoform 3 NP_001280162.1 (SEQ ID NO: 333)

1 mrgapgncvg aeqalarrkr aqtvairghp rppgppgdtr aesppdplqs agvlevgagp

61 rlprppregs tpgiktngae rspqspagrr adaellhvhh aghdlqeprp rv

Cancer/testis antigen IB NP_001318.1 (SEQ ID NO: 334)

1 mqaegrgtgg stgdadgpgg pgipdgpggn aggpgeagat ggrgprgaga arasgpggga

61 prgphggaas glngccrcga rgpesrllef ylampfatpm eaelarrsla qdapplpvpg

121 vllkeftvsg niltirltaa dhrqlqlsis sclqqlsllm witqcflpvf laqppsgqrr

Opioid growth factor receptor NP_031372.2 (SEQ ID NO: 335)

1 mddpdcdstw eedeedaeda ededeedgea agardadagd edeeseepra arpssfqsrm

61 tgsrnwratr dmcryrhnyp dlverdcngd tpnlsfyrne irflpngcfi edilqnwtdn

121 ydllednhsy iqwlfplrep gvnwhakplt Irevevfkss qeiqerlvra yelmlgfygi

181 rledrgtgtv graqnyqkrf qnlnwrshnn Iritrilksl gelglehfqa plvrffleet

241 Ivrrelpgvr qsaldyfmfa vrcrhqrrql vhfawehfrp rckfvwgpqd klrrfkpssl

301 phplegsrkv eeegspgdpd heastqgrtc gpehskgggr vdegpqprsv epqdagpler

361 sqgdeagghg edrpeplspk eskkrklels rreqpptepg pqsaseveki alnlegcals

421 qgslrtgtqe vggqdpgeav qpcrqplgar vadkvrkrrk vdegagdsaa vasggaqtla

481 lagspapsgh pkaghsengv eedtegrtgp kegtpgspse tpgpspagpa gdepaespse

541 tpgprpagpa gdepaespse tpgprpagpa gdepaespse tpgpspagpt rdepaespse

601 tpgprpagpa gdepaespse tpgprpagpa gdepaespse tpgpspagpt rdepakagea

661 aelqdaeves saksgkp

P antigen family member 4 NP_001305806.1, NP_008934.1 (SEQ ID NO: 336) 1 msarvrsrsr grgdgqeapd vvafvapges qqeepptdnq diepgqereg tppieerkve 61 gdcqemdlek trsergdgsd vkektppnpk haktkeagdg qp

Paired box protein Pax-3, isoform PAX3a NP_000429.2 (SEQ ID NO: 337)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv 61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee 121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees 181 ekkakhsidg ilsergkrwr Igrrtcwvtw rasas

Paired box protein Pax-3, isoform PAX3i NP_001120838.1 (SEQ ID NO: 338)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkvtt pdvekkieey

121 krenpgmfsw eirdkllkda vcdrntvpsv ssisrilrsk fgkgeeeead lerkeaeese

181 kkakhsidgi Iserasapqs degsdidsep dlplkrkqrr srttftaeql eelerafert

241 hypdiytree laqrakltea rvqvwfsnrr arwrkqagan qlmafnhlip ggfpptampt

301 Iptyqlsets yqptsipqav sdpsstvhrp qplppstvhq stipsnpdss sayclpstrh

361 gfssytdsfv ppsgpsnpmn ptignglspq vmglltnhgg vphqpqtdya Ispltgglep

421 tttvsascsq rldhmkslds Iptsqsycpp tysttgysmd pvtgyqygqy gqsafhylkp

481 dia

Paired box protein Pax-3, isoform PAX3b NP_039230.1 (SEQ ID NO: 339)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilsergkalv sgvssh

Paired box protein Pax-3, isoform PAX3 NP_852122.1 (SEQ ID NO: 340)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilserasapq sdegsdidse pdlplkrkqr rsrttftaeq leelerafer

241 thypdiytre elaqraklte arvqvwfsnr rarwrkqaga nqlmafnhli pggfpptamp

301 tlptyqlset syqptsipqa vsdpsstvhr pqplppstvh qstipsnpds ssayclpstr

361 hgfssytdsf vppsgpsnpm nptignglsp qvmglltnhg gvphqpqtdy alspltggle

421 ptttvsascs qrldhmksld slptsqsycp ptysttgysm dpvtgyqygq ygqskpwtf

Paired box protein Pax-3, isoform PAX3d NP_852123.1 (SEQ ID NO: 341)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilserasapq sdegsdidse pdlplkrkqr rsrttftaeq leelerafer

241 thypdiytre elaqraklte arvqvwfsnr rarwrkqaga nqlmafnhli pggfpptamp

301 tlptyqlset syqptsipqa vsdpsstvhr pqplppstvh qstipsnpds ssayclpstr

361 hgfssytdsf vppsgpsnpm nptignglsp qvmglltnhg gvphqpqtdy alspltggle

421 ptttvsascs qrldhmksld slptsqsycp ptysttgysm dpvtgyqygq ygqsafhylk

481 pdia

Paired box protein Pax-3, isoform PAX3e NP_852124.1 (SEQ ID NO: 342)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilserasapq sdegsdidse pdlplkrkqr rsrttftaeq leelerafer

241 thypdiytre elaqraklte arvqvwfsnr rarwrkqaga nqlmafnhli pggfpptamp

301 tlptyqlset syqptsipqa vsdpsstvhr pqplppstvh qstipsnpds ssayclpstr

361 hgfssytdsf vppsgpsnpm nptignglsp qvmglltnhg gvphqpqtdy alspltggle 421 ptttvsascs qrldhmksld slptsqsycp ptysttgysm dpvtgyqygq ygqsafhylk

481 pdiawfqill ntfdkssgee edleq

Paired box protein Pax-3, isoform PAX3h NP_852125.1 (SEQ ID NO: 343)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv

61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilserasapq sdegsdidse pdlplkrkqr rsrttftaeq leelerafer

241 thypdiytre elaqraklte arvqvwfsnr rarwrkqaga nqlmafnhli pggfpptamp

301 tlptyqlset syqptsipqa vsdpsstvhr pqplppstvh qstipsnpds ssayclpstr

361 hgfssytdsf vppsgpsnpm nptignglsp qvpfiissqi slgfksf

Paired box protein Pax-3, isoform PAX3g NP_852126.1 (SEQ ID NO: 344)

1 mttlagavpr mmrpgpgqny prsgfplevs tplgqgrvnq Iggvfingrp Ipnhirhkiv 61 emahhgirpc visrqlrvsh gcvskilcry qetgsirpga iggskpkqvt tpdvekkiee

121 ykrenpgmfs weirdkllkd avcdrntvps vssisrilrs kfgkgeeeea dlerkeaees

181 ekkakhsidg ilserasapq sdegsdidse pdlplkrkqr rsrttftaeq leelerafer

241 thypdiytre elaqraklte arvqvwfsnr rarwrkqaga nqlmafnhli pggfpptamp

301 tlptyqlset syqptsipqa vsdpsstvhr pqplppstvh qstipsnpds ssayclpstr

361 hgfssytdsf vppsgpsnpm nptignglsp qvpfiissqi srk

Paired box protein Pax-5, isoform 1 NP_057953.1 (SEQ ID NO: 345)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq tteysamasl agglddmkan lasptpadig ssvpgpqsyp

301 ivtgrdlast tlpgypphvp pagqgsysap tltgmvpgse fsgspyshpq yssyndswrf

361 pnpgllgspy yysaaargaa ppaaataydr h

Paired box protein Pax-5, isoform 2 NP_001267476.1 (SEQ ID NO: 346)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq tteysamasl agglddmkan lasptpadig ssvpgpqsyp

301 ivtgsefsgs pyshpqyssy ndswrfpnpg llgspyyysa aargaappaa ataydrh

Paired box protein Pax-5, isoform 3 NP_001267477.1 (SEQ ID NO: 347)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq tteysamasl agglddmkan lasptpadig ssvpgpqsyp

301 ivtgrdlast tlpgypphvp pagqgsysap tltgmvpgsp yyysaaarga appaaatayd

361 rh

Paired box protein Pax-5, isoform 4 NP_001267478.1 (SEQ ID NO: 348)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq gvsfpgvpta tlsiprtttp ggsptrgcla pptiialppe

301 epphlqpplp mtvtdpwsqa gtkh

Paired box protein Pax-5, isoform 5 NP_001267479.1 (SEQ ID NO: 349)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq apptiialpp eepphlqppl pmtvtdpwsq agtkh

Paired box protein Pax-5, isoform 6 NP_001267480.1 (SEQ ID NO: 350)

1 mfaweirdrl laervcdndt vpsvssinri irtkvqqppn qpvpasshsi vstgsvtqvs

61 svstdsagss ysisgilgit spsadtnkrk rdegiqespv pnghslpgrd flrkqmrgdl 121 ftqqqlevld rvferqhysd iftttepikp eqtteysama slagglddmk anlasptpad 181 igssvpgpqs ypivtgspyy ysaaargaap paaataydrh

Paired box protein Pax-5, isoform 7 NP_001267481.1 (SEQ ID NO: 351)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsivs tgsvtqvssv stdsagssys

181 isgilgitsp sadtnkrkrd egiqespvpn ghslpgrdfl rkqmrgdlft qqqlevldrv

241 ferqhysdif tttepikpeq tteysamasl agglddmkan lasptpadig ssvpgpqsyp

301 ivtgspyyys aaargaappa aataydrh

Paired box protein Pax-5, isoform 8 NP_001267482.1 (SEQ ID NO: 352)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsigi qespvpnghs Ipgrdflrkq

181 mrgdlftqqq levldrvfer qhysdifttt epikpeqtte ysamaslagg Iddmkanlas

241 ptpadigssv pgpqsypivt grdlasttlp gypphvppag qgsysaptlt gmvpgspyyy

301 saaargaapp aaataydrh Paired box protein Pax-5, isoform 9 NP_001267483.1 (SEQ ID NO: 353)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg ryyetgsikp gviggskpkv atpkvvekia eykrqnptmf aweirdrlla

121 ervcdndtvp svssinriir tkvqqppnqp vpasshsigi qespvpnghs Ipgrdflrkq

181 mrgdlftqqq levldrvfer qhysdifttt epikpeqtte ysamaslagg Iddmkanlas

241 ptpadigssv pgpqsypivt grdlasttlp gypphvppag qgsysaptlt gmvpgsefsg

301 spyshpqyss yndswrfpnp gllgspyyys aaargaappa aataydrh

Paired box protein Pax-5, isoform 10 NP_001267484.1 (SEQ ID NO: 354)

1 mdleknyptp rtsrtghggv nqlggvfvng rplpdvvrqr ivelahqgvr pcdisrqlrv

61 shgcvskilg riirtkvqqp pnqpvpassh sivstgsvtq vssvstdsag ssysisgilg

121 itspsadtnk rkrdegiqes pvpnghslpg rdflrkqmrg dlftqqqlev Idrvferqhy

181 sdiftttepi kpeqtteysa maslaggldd mkanlasptp adigssvpgp qsypivtgse

241 fsgspyshpq yssyndswrf pnpgllgspy yysaaargaa ppaaataydr h

Paired box protein Pax-5, isoform 11 NP_001267485.1 (SEQ ID NO: 355)

1 mfaweirdrl laervcdndt vpsvssinri irtkvqqppn qpvpasshsi vstgsvtqvs 61 svstdsagss ysisgilgit spsadtnkrk rdegiqespv pnghslpgrd flrkqmrgdl 121 ftqqqlevld rvferqhysd iftttepikp eqtteysama slagglddmk anlasptpad 181 igssvpgpqs ypivtgrdla sttlpgypph vppagqgsys aptltgmvpg sefsgspysh 241 pqyssyndsw rfpnpgllgs pyyysaaarg aappaaatay drh

Platelet-derived growth factor receptor beta, isoform 1 NP_002600.1 (SEQ ID NO: 356)

1 mrlpgampal alkgelllls lllllepqis qglvvtppgp elvlnvsstf vltcsgsapv

61 vwermsqepp qemakaqdgt fssvltltnl tgldtgeyfc thndsrglet derkrlyifv

121 pdptvgflpn daeelfiflt eiteitipcr vtdpqlvvtl hekkgdvalp vpydhqrgfs

181 gifedrsyic kttigdrevd sdayyvyrlq vssinvsvna vqtvvrqgen itlmcivign

241 evvnfewtyp rkesgrlvep vtdflldmpy hirsilhips aeledsgtyt cnvtesvndh

301 qdekainitv vesgyvrllg evgtlqfael hrsrtlqvvf eayppptvlw fkdnrtlgds

361 sageialstr nvsetryvse Itlvrvkvae aghytmrafh edaevqlsfq Iqinvpvrvl

421 elseshpdsg eqtvrcrgrg mpqpniiwsa crdlkrcpre Ipptllgnss eeesqletnv

481 tyweeeqefe vvstlrlqhv drplsvrctl rnavgqdtqe vivvphslpf kvvvisaila

541 Ivvltiisli ilimlwqkkp ryeirwkvie svssdgheyi yvdpmqlpyd stwelprdql

601 vlgrtlgsga fgqvveatah glshsqatmk vavkmlksta rssekqalms elkimshlgp

661 hlnvvnllga ctkggpiyii teycrygdlv dylhrnkhtf Iqhhsdkrrp psaelysnal

721 pvglplpshv sltgesdggy mdmskdesvd yvpmldmkgd vkyadiessn ymapydnyvp

781 sapertcrat linespvlsy mdlvgfsyqv angmeflask ncvhrdlaar nvlicegklv

841 kicdfglard imrdsnyisk gstflplkwm apesifnsly ttlsdvwsfg illweiftlg

901 gtpypelpmn eqfynaikrg yrmaqpahas deiyeimqkc weekfeirpp fsqlvlller

961 llgegykkky qqvdeeflrs dhpailrsqa rlpgfhglrs pldtssvlyt avqpnegdnd

1021 yiiplpdpkp evadegpleg spslasstln evntsstisc dsplepqdep epepqlelqv

1081 epepeleqlp dsgcpaprae aedsfl

Platelet-derived growth factor receptor beta, isoform 2 NP_001341945.1 (SEQ ID NO: 357)

1 msqeppqema kaqdgtfssv Itltnltgld tgeyfcthnd srgletderk rlyifvpdpt

61 vgflpndaee Ififlteite itipcrvtdp qlvvtlhekk gdvalpvpyd hqrgfsgife

121 drsyicktti gdrevdsday yvyrlqvssi nvsvnavqtv vrqgenitlm civignevvn

181 fewtyprkes grlvepvtdf lldmpyhirs ilhipsaele dsgtytcnvt esvndhqdek

241 ainitvvesg yvrllgevgt Iqfaelhrsr tlqvvfeayp pptvlwfkdn rtlgdssage

301 ialstrnvse tryvseltlv rvkvaeaghy tmrafhedae vqlsfqlqin vpvrvlelse

361 shpdsgeqtv rcrgrgmpqp niiwsacrdl krcprelppt llgnsseees qletnvtywe

421 eeqefevvst Irlqhvdrpl svrctlrnav gqdtqevivv phslpfkvvv isailalvvl

481 tiisliilim Iwqkkpryei rwkviesvss dgheyiyvdp mqlpydstwe Iprdqlvlgr

541 tlgsgafgqv veatahglsh sqatmkvavk mlkstarsse kqalmselki mshlgphlnv

601 vnllgactkg gpiyiiteyc rygdlvdylh rnkhtflqhh sdkrrppsae lysnalpvgl

661 plpshvsltg esdggymdms kdesvdyvpm Idmkgdvkya diessnymap ydnyvpsape

721 rtcratline spvlsymdlv gfsyqvangm eflaskncvh rdlaarnvli cegklvkicd

781 fglardimrd snyiskgstf Iplkwmapes ifnslyttls dvwsfgillw eiftlggtpy

841 pelpmneqfy naikrgyrma qpahasdeiy eimqkcweek feirppfsql vlllerllge

901 gykkkyqqvd eeflrsdhpa ilrsqarlpg fhglrspldt ssvlytavqp negdndyiip

961 Ipdpkpevad egplegspsl asstlnevnt sstiscdspl epqdepepep qlelqvepep

1021 eleqlpdsgc papraeaeds fl Platelet-derived growth factor receptor beta, isoform 3 NP_001341946.1 (SEQ ID NO: 358)

1 mitnvaflvs Irteatsakp plgtgrwilm ptmstdsrvs plsglmlsrv ssinvsvnav

61 qtvvrqgeni tlmcivigne vvnfewtypr kesgrlvepv tdflldmpyh irsilhipsa

121 eledsgtytc nvtesvndhq dekainitvv esgyvrllge vgtlqfaelh rsrtlqvvfe

181 ayppptvlwf kdnrtlgdss ageialstrn vsetryvsel tlvrvkvaea ghytmrafhe

241 daevqlsfql qinvpvrvle Iseshpdsge qtvrcrgrgm pqpniiwsac rdlkrcprel

301 pptllgnsse eesqletnvt yweeeqefev vstlrlqhvd rplsvrctlr navgqdtqev

361 ivvphslpfk vvvisailal vvltiislii limlwqkkpr yeirwkvies vssdgheyiy

421 vdpmqlpyds twelprdqlv Igrtlgsgaf gqvveatahg Ishsqatmkv avkmlkstar

481 ssekqalmse Ikimshlgph Invvnllgac tkggpiyiit eycrygdlvd ylhrnkhtfl

541 qhhsdkrrpp saelysnalp vglplpshvs Itgesdggym dmskdesvdy vpmldmkgdv

601 kyadiessny mapydnyvps apertcratl inespvlsym dlvgfsyqva ngmeflaskn

661 cvhrdlaarn vlicegklvk icdfglardi mrdsnyiskg stflplkwma pesifnslyt

721 tlsdvwsfgi llweiftlgg tpypelpmne qfynaikrgy rmaqpahasd eiyeimqkcw

781 eekfeirppf sqlvlllerl Igegykkkyq qvdeeflrsd hpailrsqar Ipgfhglrsp

841 Idtssvlyta vqpnegdndy iiplpdpkpe vadegplegs pslasstlne vntsstiscd

901 splepqdepe pepqlelqve pepeleqlpd sgcpapraea edsfl

Placenta-specific protein 1 precursor NP_001303816.1, NP_001303817.1, NP_001303818.1, NP_068568.1 (SEQ ID NO: 359)

1 mkvfkfiglm illtsafsag sgqspmtvlc sidwfmvtvh pfmlnndvcv hfhelhlglg 61 cppnhvqpha yqftyrvtec girakavsqd mviysteihy sskgtpskfv ipvscaapqk 121 spwltkpcsm rvasksrata qkdekcyevf slsqssqrpn cdcppcvfse eehtqvpchq 181 agaqeaqplq pshfldised wslhtddmig sm

Melanoma antigen preferentially expressed in tumors, isoform a

NP_001278644.1 , NP_001278645.1 , NP_006106.1, NP_996836.1, NP_996837.1, NP_996838.1, NP_996839.1 (SEQ ID NO: 360)

1 merrrlwgsi qsryismsvw tsprrlvela gqsllkdeal aiaalellpr elfpplfmaa

61 fdgrhsqtlk amvqawpftc Iplgvlmkgq hlhletfkav Idgldvllaq evrprrwklq

121 vldlrknshq dfwtvwsgnr aslysfpepe aaqpmtkkrk vdglsteaeq pfipvevlvd

181 Iflkegacde Ifsyliekvk rkknvlrlcc kklkifampm qdikmilkmv qldsiedlev

241 tctwklptla kfspylgqmi nlrrlllshi hassyispek eeqyiaqfts qflslqclqa

301 lyvdslfflr grldqllrhv mnpletlsit ncrlsegdvm hlsqspsvsq Isvlslsgvm

361 ltdvspeplq allerasatl qdlvfdecgi tddqllallp slshcsqltt Isfygnsisi

421 salqsllqhl iglsnlthvl ypvplesyed ihgtlhlerl aylharlrel Icelgrpsmv

481 wlsanpcphc gdrtfydpep ilcpcfmpn

Melanoma antigen preferentially expressed in tumors, isoform b

NP_001278646.1, NP_001278648.1 , NP_001305055.1, NP_001305056.1 (SEQ ID NO: 361)

1 msvwtsprrl velagqsllk dealaiaale llprelfppl fmaafdgrhs qtlkamvqaw

61 pftclplgvl mkgqhlhlet fkavldgldv llaqevrprr wklqvldlrk nshqdfwtvw

121 sgnraslysf pepeaaqpmt kkrkvdglst eaeqpfipve vlvdlflkeg acdelfsyli

181 ekvkrkknvl rlcckklkif ampmqdikmi Ikmvqldsie dlevtctwkl ptlakfspyl

241 gqminlrrll Ishihassyi spekeeqyia qftsqflslq clqalyvdsl fflrgrldql

301 Irhvmnplet Isitncrlse gdvmhlsqsp svsqlsvlsl sgvmltdvsp eplqallera

361 satlqdlvfd ecgitddqll allpslshcs qlttlsfygn sisisalqsl Iqhliglsnl

421 thvlypvple syedihgtlh lerlaylhar Irellcelgr psmvwlsanp cphcgdrtfy

481 dpepilcpcf mpn

Phosphatidylinositol 3 , 4 , 5-triphosphate-dependent Rac exchanger 2 protein, isoform a NP_079146.2 (SEQ ID NO: 362)

1 msedsrgdsr aesakdlekq Irlrvcvlse Iqkterdyvg tleflvsafl hrmnqcaask

61 vdknvteetv kmlfsniedi lavhkeflkv veeclhpepn aqqevgtcfl hfkdkfriyd

121 eycsnhekaq klllelnkir tirtfllncm llggrkntdv plegylvtpi qrickyplil

181 kellkrtprk hsdyaavmea Iqamkavcsn ineakrqmek levleewqsh iegwegsnit

241 dtctemlmcg vllkissgni qervfflfdn llvyckrkhr rlknskastd ghrylfrgri

301 ntevmevenv ddgtadfhss ghivvngwki hntaknkwfv cmaktpeekh ewfeailker

361 errkglklgm eqdtwvmise qgeklykmmc rqgnlikdrk rklttfpkcf Igsefvswll

421 eigeihrpee gvhlgqalle ngiihhvtdk hqfkpeqmly rfryddgtfy prnemqdvis

481 kgvrlycrlh slftpvirdk dyhlrtyksv vmanklidwl iaqgdcrtre eamifgvglc

541 dngfmhhvle ksefkdepll frffsdeeme gsnmkhrlmk hdlkvvenvi akslliksne

601 gsygfgledk nkvpiiklve kgsnaemagm evgkkifain gdlvfmrpfn evdcflkscl 661 nsrkplrvlv stkpretvki pdsadglgfq irgfgpsvvh avgrgtvaaa aglhpgqcii

721 kvnginvske thasviahvt acrkyrrptk qdsiqwvyns iesaqedlqk shskppgdea

781 gdafdckvee vidkfntmai idgkkehvsl tvdnvhleyg vvyeydstag ikcnvvekmi

841 epkgffslta kilealaksd ehfvqnctsl nslneviptd Iqskfsalcs eriehlcqri

901 ssykkfsrvl knrawptfkq akskisplhs sdfcptnchv nvmevsypkt stslgsafgv

961 qldsrkhnsh dkenksseqg klspmvyiqh tittmaapsg Islgqqdghg Iryllkeedl

1021 etqdiyqkll gklqtalkev emcvcqiddl Issityspkl erktsegiip tdsdnekger

1081 nskrvcfnva gdeqedsghd tisnrdsysd cnsnrnsias ftsicssqcs syfhsdemds

1141 gdelplsvri shdkqdkihs clehlfsqvd sitnllkgqa vvrafdqtky Itpgrglqef

1201 qqemepklsc pkrlrlhikq dpwnlpssvr tlaqnirkfv eevkcrllla lleysdsetq

1261 Irrdmvfcqt Ivatvcafse qlmaalnqmf dnskenemet weasrrwldq ianagvlfhf

1321 qsllspnltd eqamledtlv alfdlekvsf yfkpseeepl vanvpltyqa egsrqalkvy

1381 fyidsyhfeq Ipqrlknggg fkihpvlfaq alesmegyyy rdnvsveefq aqinaaslek

1441 vkqynqklra fyldksnspp nstskaayvd klmrplnald elyrlvasfi rskrtaacan

1501 tacsasgvgl Isvsselcnr Igachiimcs sgvhrctlsv tleqaiilar shglppryim

1561 qatdvmrkqg arvqntaknl gvrdrtpqsa prlyklcepp ppagee

Phosphatidylinositol 3,4, 5-triphosphate-dependent Rac exchanger 2 protein, isoform b NP_079446.3 (SEQ ID NO: 363)

1 msedsrgdsr aesakdlekq Irlrvcvlse Iqkterdyvg tleflvsafl hrmnqcaask

61 vdknvteetv kmlfsniedi lavhkeflkv veeclhpepn aqqevgtcfl hfkdkfriyd

121 eycsnhekaq klllelnkir tirtfllncm llggrkntdv plegylvtpi qrickyplil

181 kellkrtprk hsdyaavmea Iqamkavcsn ineakrqmek levleewqsh iegwegsnit

241 dtctemlmcg vllkissgni qervfflfdn llvyckrkhr rlknskastd ghrylfrgri

301 ntevmevenv ddgtadfhss ghivvngwki hntaknkwfv cmaktpeekh ewfeailker

361 errkglklgm eqdtwvmise qgeklykmmc rqgnlikdrk rklttfpkcf Igsefvswll

421 eigeihrpee gvhlgqalle ngiihhvtdk hqfkpeqmly rfryddgtfy prnemqdvis

481 kgvrlycrlh slftpvirdk dyhlrtyksv vmanklidwl iaqgdcrtre eamifgvglc

541 dngfmhhvle ksefkdepll frffsdeeme gsnmkhrlmk hdlkvvenvi akslliksne

601 gsygfgledk nkvpiiklve kgsnaemagm evgkkifain gdlvfmrpfn evdcflkscl

661 nsrkplrvlv stkpretvki pdsadglgfq irgfgpsvvh avgrgtvaaa aglhpgqcii

721 kvnginvske thasviahvt acrkyrrptk qdsiqwvyns iesaqedlqk shskppgdea

781 gdafdckvee vidkfntmai idgkkehvsl tvdnvhleyg vvyeydstag ikcnvvekmi

841 epkgffslta kilealaksd ehfvqnctsl nslneviptd Iqskfsalcs eriehlcqri

901 ssykkvqase rfynftarha vwehsfdlhs vsstfpvpvt meflllpppl Igisqdgrqh

961 cipedlpsqe mllaerapv

Protamine-2, isoform 1 NP_002753.2 (SEQ ID NO: 364)

1 mvryrvrsls ershevyrqq Ihgqeqghhg qeeqglspeh vevyerthgq shyrrrhcsr 61 rrlhrihrrq hrscrrrkrr scrhrrrhrr gcrtrkrtcr rh

Protamine-2, isoform 2 NP_001273285.1 (SEQ ID NO: 365)

1 mvryrvrsls ershevyrqq Ihgqeqghhg qeeqglspeh vevyerthgq shyrrrhcsr 61 rrlhrihrrq hrscrrrkrr scrhrrrhrr eslgdplnqn flsqkaaepg rehaegtklp 121 gpltpswklr ksrpkhqvrp

Protamine-2, isoform 3 NP_001273286.1 (SEQ ID NO: 366)

1 mvryrvrsls ershevyrqq Ihgqeqghhg qeeqglspeh vevyerthgq shyrrrhcsr 61 rrlhrihrrq hrscrrh

Protamine-2, isoform 4 NP_001273287.1 (SEQ ID NO: 367)

1 mvryrvrsls ershevyrqq Ihgqeqghhg qeeqglspeh vevyerthgq shyrrrhcsr 61 rrlhrihrrq hrscrrrkrr scrhrrrhrr epgrehaegt klpgpltpsw klrksrpkhq 121 vrp

Protamine-2, isoform 5 NP_001273288.1 (SEQ ID NO: 368)

1 mvryrvrsls ershevyrqq Ihgqeqghhg qeeqglspeh vevyerthgq shyrrrhcsr 61 rrlhrihrrq hrscrrrkrr scrhrrrhrr glpapppcpa cp

Progranulin NP_002078.1 (SEQ ID NO: 369)

1 mwtlvswval taglvagtrc pdgqfcpvac cldpggasys ccrplldkwp ttlsrhlggp

61 cqvdahcsag hsciftvsgt ssccpfpeav acgdghhccp rgfhcsadgr scfqrsgnns

121 vgaiqcpdsq fecpdfstcc vmvdgswgcc pmpqascced rvhccphgaf cdlvhtrcit

181 ptgthplakk Ipaqrtnrav alsssvmcpd arsrcpdgst ccelpsgkyg ccpmpnatcc

241 sdhlhccpqd tvcdliqskc Iskenattdl Itklpahtvg dvkcdmevsc pdgytccrlq

301 sgawgccpft qavccedhih ccpagftcdt qkgtceqgph qvpwmekapa hlslpdpqal

361 krdvpcdnvs scpssdtccq Itsgewgccp ipeavccsdh qhccpqgytc vaegqcqrgs

421 eivaglekmp arraslshpr digcdqhtsc pvgqtccpsl ggswaccqlp havccedrqh 481 ccpagytcnv karscekevv saqpatflar sphvgvkdve cgeghfchdn qtccrdnrqg

541 waccpyrqgv ccadrrhccp agfrcaargt kclrreaprw daplrdpalr qll

Myeloblastin precursor NP_002768.3 (SEQ ID NO: 370)

1 mahrppspal asvllallls gaaraaeivg gheaqphsrp ymaslqmrgn pgshfcggtl

61 ihpsfvltaa hclrdipqrl vnvvlgahnv rtqeptqqhf svaqvflnny daenklndvl

121 liqlsspanl sasvatvqlp qqdqpvphgt qclamgwgrv gahdppaqvl qelnvtvvtf

181 fcrphnictf vprrkagicf gdsggplicd giiqgidsfv iwgcatrlfp dfftrvalyv

241 dwirstlrrv eakgrp

Prostate stem cell antigen preportein NP_005663.2 (SEQ ID NO: 371)

1 maglalqpgt allcysckaq vsnedclqve nctqlgeqcw tariravgll tviskgcsln 61 cvddsqdyyv gkknitccdt dlcnasgaha Iqpaaailal Ipalglllwg pgql Ras-related 03 botulinum toxin substrate 1 isoform Raclb NP_061485.1 (SEQ ID NO: 372)

1 mqaikcvvvg dgavgktcll isyttnafpg eyiptvfdny sanvmvdgkp vnlglwdtag

61 qedydrlrpl sypqtvgety gkditsrgkd kpiadvflic fslvspasfe nvrakwypev

121 rhhcpntpii Ivgtkldlrd dkdtieklke kkltpitypq glamakeiga vkylecsalt

181 qrglktvfde airavlcppp vkkrkrkcll 1

Regenerating islet-derived protein 3-alpha precursor NP_002571.1, NP_620354.1, NP_620355.1 (SEQ ID NO: 373)

1 mlppmalpsv swmllsclml Isqvqgeepq relpsarirc pkgskaygsh cyalflspks

61 wtdadlacqk rpsgnlvsvl sgaegsfvss Ivksignsys yvwiglhdpt qgtepngegw

121 ewsssdvmny fawernpsti sspghcasls rstaflrwkd yncnvrlpyv ckftd

Regulator of G-protein signaling 5, isoform 1 NP_003608.1 (SEQ ID NO: 374)

1 mckglaalph sclerakeik iklgillqkp dsvgdlvipy nekpekpakt qktsldealq

61 wrdsldkllq nnyglasfks flksefseen lefwiacedy kkikspakma ekakqiyeef

121 iqteapkevn idhftkditm knlvepslss fdmaqkriha Imekdslprf vrsefyqeli

181 k

Regulator of G-protein signaling 5, isoform 2 NP_001182232.1, NP_001241677.1 (SEQ ID NO: 375)

1 maekakqiye efiqteapke vnidhftkdi tmknlvepsl ssfdmaqkri halmekdslp 61 rfvrsefyqe lik

Regulator of G-protein signaling 5, isoform 3 NP_001241678.1 (SEQ ID NO: 376)

1 mckglaalph sclerakeik iklgillqkp dsvgdlvipy nekpekpakt qktsldealq

61 wrdsldkllq nnyglasfks flksefseen lefwiacedy kkikspakma ekakqiyeef

121 iqteapkevg Iwvnidhftk ditmknlvep slssfdmaqk rihalmekds Iprfvrsefy

181 qelik

Rho-related GTP-binding protein RhoC precursor NP_001036143.1 , NP_001036144.1, NP_786886.1 (SEQ ID NO: 377)

1 maairkklvi vgdgacgktc llivfskdqf pevyvptvfe nyiadievdg kqvelalwdt 61 agqedydrlr plsypdtdvi Imcfsidspd slenipekwt pevkhfcpnv piilvgnkkd 121 Irqdehtrre lakmkqepvr seegrdmanr isafgylecs aktkegvrev fematraglq 181 vrknkrrrgc pil

Sarcoma antigen 1 NP_061136.2 (SEQ ID NO: 378)

1 mqasplqtsq ptppeelhaa ayvftndgqq mrsdevnlva tghqskkkhs rkskrhsssk

61 rrksmsswld kqedaavths iceerinngq pvadnvlsta ppwpdatiah nireermeng

121 qsrtdkvlst appqlvhmaa agipsmstrd Ihstvthnir eermengqpq pdnvlstgpt

181 glinmaatpi pamsardlya tvthnvceqk menvqpapdn vlltlrprri nmtdtgispm

241 strdpyatit ynvpeekmek gqpqpdnils tastglinva gagtpaistn glystvphnv

301 ceekmendqp qpnnvlstvq pviiyltatg ipgmntrdqy atithnvcee rvvnnqplps

361 nalstvlpgl aylatadmpa mstrdqhati ihnlreekkd nsqptpdnvl savtpelinl

421 agagippmst rdqyatvnhh vhearmengq rkqdnvlsnv Isglinmaga sipamssrdl

481 yatithsvre ekmesgkpqt dkvisndapq Ighmaaggip smstkdlyat vtqnvheerm

541 ennqpqpsyd Istvlpglty Itvagipams trdqyatvth nvheekikng qaasdnvfst

601 vppafinmaa tgvssmstrd qyaavthnir eekinnsqpa pgnilstapp wlrhmaaagi

661 sstitrdlyv tathsvheek mtngqqapdn slstvppgci nlsgagiscr strdlyatvi

721 hdiqeeemen dqtppdgfls nsdspelinm tghcmppnal dsfshdftsl skdellykpd

781 snefavgtkn ysvsagdppv tvmslvetvp ntpqispama kkinddikyq Imkevrrfgq

841 nyerifille evqgsmkvkr qfveftikea arfkkvvliq qlekalkeid shchlrkvkh

901 mrkr

Squamous cell carcinoma antigen recognized by T-cells 3 NP_055521.1 (SEQ ID NO: 379) 1 mataaetsas epeaeskagp kadgeedevk aartrrkvls ravaaatykt mgpawdqqee

61 gvsesdgdey amassaessp geyeweydee eeknqleier leeqlsinvy dynchvdlir

121 llrlegeltk vrmarqkmse ifplteelwl ewlhdeisma qdgldrehvy dlfekavkdy

181 icpniwleyg qysvggigqk gglekvrsvf eralssvglh mtkglalwea yrefesaive

241 aarlekvhsl frrqlaiply dmeatfaeye ewsedpipes viqnynkalq qlekykpyee

301 allqaeaprl aeyqayidfe mkigdpariq liferalven clvpdlwiry sqyldrqlkv

361 kdlvlsvhnr airncpwtva Iwsryllame rhgvdhqvis vtfekalnag fiqatdyvei

421 wqayldylrr rvdfkqdssk eleelraaft raleylkqev eerfnesgdp scvimqnwar

481 iearlcnnmq karelwdsim trgnakyanm wleyynlera hgdtqhcrka Ihravqctsd

541 ypehvcevll tmertegsle dwdiavqkte trlarvneqr mkaaekeaal vqqeeekaeq

601 rkraraekka Ikkkkkirgp ekrgadedde kewgddeeeq pskrrrvens ipaagetqnv

661 evaagpagkc aavdveppsk qkekaaslkr dmpkvlhdss kdsitvfvsn Ipysmqepdt

721 klrplfeacg evvqirpifs nrgdfrgycy vefkeeksal qalemdrksv egrpmfvspc

781 vdksknpdfk vfrystslek hklfisglpf sctkeeleei ckahgtvkdl rlvtnragkp

841 kglayveyen esqasqavmk mdgmtikeni ikvaisnppq rkvpekpetr kapggpmllp

901 qtygargkgr tqlsllpral qrpsaaapqa engpaaapav aapaateapk msnadfaklf

961 Irk

Secretory leukocyte protein inhibitor NP_003055.1 (SEQ ID NO: 380)

1 mkssglfpfl vllalgtlap wavegsgksf kagvcppkks aqclrykkpe cqsdwqcpgk 61 krccpdtcgi kcldpvdtpn ptrrkpgkcp vtygqclmln ppnfcemdgq ckrdlkccmg 121 mcgkscvspv ka

Transcription factor SOX-10 NP_008872.1 (SEQ ID NO: 381)

1 maeeqdlsev elspvgseep rclspgsaps Igpdgggggs glraspgpge Igkvkkeqqd

61 geadddkfpv cireavsqvl sgydwtlvpm pvrvngasks kphvkrpmna fmvwaqaarr

121 kladqyphlh naelsktlgk Iwrllnesdk rpfieeaerl rmqhkkdhpd ykyqprrrkn

181 gkaaqgeaec pggeaeqggt aaiqahyksa hldhrhpgeg spmsdgnpeh psgqshgppt

241 ppttpktelq sgkadpkrdg rsmgeggkph idfgnvdige ishevmsnme tfdvaeldqy

301 Ippnghpghv ssysaagygl gsalavasgh sawiskppgv alptvsppgv dakaqvktet

361 agpqgpphyt dqpstsqiay tslslphygs afpsisrpqf dysdhqpsgp yyghsgqasg

421 lysafsymgp sqrplytais dpspsgpqsh spthweqpvy ttlsrp

Sperm surface protein Spl7 NP_059121.1 (SEQ ID NO: 382)

1 msipfsnthy ripqgfgnll egltreilre qpdnipafaa ayfesllekr ektnfdpaew 61 gskvedrfyn nhafeeqepp eksdpkqees qisgkeeets vtildsseed kekeevaavk 121 iqaafrghia reeakkmktn slqneekeen k

Protein SSX2, isoform a NP_003138.3 (SEQ ID NO: 383)

1 mngddafarr ptvgaqipek iqkafddiak yfskeewekm kasekifyvy mkrkyeamtk 61 Igfkatlppf mcnkraedfq gndldndpnr gnqverpqmt fgrlqgispk impkkpaeeg 121 ndseevpeas gpqndgkelc ppgkpttsek ihersgnrea qekeerrgta hrwssqnthn 181 igrfslstsm gavhgtpkti thnrdpkggn mpgptdcvre nsw

Protein SSX2, isoform b NP_783629.1 (SEQ ID NO: 384)

1 mngddafarr ptvgaqipek iqkafddiak yfskeewekm kasekifyvy mkrkyeamtk 61 Igfkatlppf mcnkraedfq gndldndpnr gnqverpqmt fgrlqgispk impkkpaeeg 121 ndseevpeas gpqndgkelc ppgkpttsek ihersgpkrg ehawthrlre rkqlviyeei 181 sdpeedde

Protein SSX2, isoform c NP_001265626.1 (SEQ ID NO: 385)

1 mngddafarr ptvgaqipek iqkafddiak yfskeewekm kasekifyvy mkrkyeamtk 61 Igfkatlppf mcnkraedfq gndldndpnr gnqverpqmt fgrlqgispk impkkpaeeg 121 ndseevpeas gpqndgkelc ppgkpttsek ihersgnrea qekeerrgta hrwssqnthn 181 igpkrgehaw thrlrerkql viyeeisdpe edde

Lactosylceramide alpha-2 , 3-sialyltrans f erase , isoform 1 NP_003887.3 (SEQ ID NO : 386)

1 mrtkaagcae rrplqprtea aaapagramp seytyvklrs dcsrpslqwy traqskmrrp

61 slllkdilkc tllvfgvwil yilklnytte ecdmkkmhyv dpdhvkraqk yaqqvlqkec

121 rpkfaktsma llfehrysvd llpfvqkapk dseaeskydp pfgfrkfssk vqtllellpe

181 hdlpehlkak tcrrcvvigs ggilhglelg htlnqfdvvi rlnsapvegy sehvgnktti

241 rmtypegapl sdleyysndl fvavlfksvd fnwlqamvkk etlpfwvrlf fwkqvaekip

301 Iqpkhfriln pviiketafd ilqysepqsr fwgrdknvpt igviavvlat hlcdevslag

361 fgydlnqprt plhyfdsqcm aamnfqtmhn vttetkfllk Ivkegvvkdl sggidref

Lactosylceramide alpha-2, 3-sialyltransferase, isoform 2 NP_001035902.1 (SEQ ID NO: 387)

1 masvpmpsey tyvklrsdcs rpslqwytra qskmrrpsll Ikdilkctll vfgvwilyil 61 klnytteecd mkkmhyvdpd hvkraqkyaq qvlqkecrpk faktsmallf ehrysvdllp

121 fvqkapkdse aeskydppfg frkfsskvqt llellpehdl pehlkaktcr rcvvigsggi

181 Ihglelghtl nqfdvvirln sapvegyseh vgnkttirmt ypegaplsdl eyysndlfva

241 vlfksvdfnw Iqamvkketl pfwvrlffwk qvaekiplqp khfrilnpvi iketafdilq

301 ysepqsrfwg rdknvptigv iavvlathlc devslagfgy dlnqprtplh yfdsqcmaam

361 nfqtmhnvtt etkfllklvk egvvkdlsgg idref

Lactosylceramide alpha-2, 3-sialyltransferase, isoform 3 NP_001341152.1, NP_001341153.1, NP_001341155.1 , NP_001341162.1 , NP_001341163.1 , NP_001341177.1 (SEQ ID NO: 388)

1 mallfehrys vdllpfvqka pkdseaesky dppfgfrkfs skvqtllell pehdlpehlk

61 aktcrrcvvi gsggilhgle Ightlnqfdv virlnsapve gysehvgnkt tirmtypega

121 plsdleyysn dlfvavlfks vdfnwlqamv kketlpfwvr Iffwkqvaek iplqpkhfri

181 Inpviiketa fdilqysepq srfwgrdknv ptigviavvl athlcdevsl agfgydlnqp

241 rtplhyfdsq cmaamnf qtm hnvttetkfl Iklvkegvvk dlsggidref

Lactosylceramide alpha-2, 3-sialyltransferase, isoform 4 NP_001341156.1, NP_001341158.1 , NP_001341167.1 (SEQ ID NO: 389)

1 mpseytyvkl rsdcsrpslq wytraqskmr rpslllkdil kctllvfgvw ilyilklnyt

61 teecdmkkmh yvdpdhvkra qkyaqqvlqk ecrpkfakts mallfehrys vdllpfvqka

121 pkdseaesky dppfgfrkfs skvqtllell pehdlpehlk aktcrrcvvi gsggilhgle

181 Ightlnqfdv virlnsapve gysehvgnkt tirmtypega plsdleyysn dlfvavlfks

241 vdfnwlqamv kketlpfwvr Iffwkqvaek iplqpkhfri Inpviiketa fdilqysepq

301 srfwgrdknv ptigviavvl athlcdevsl agfgydlnqp rtplhyfdsq cmaamnfqtm

361 hnvttetkfl Iklvkegvvk dlsggidref

Lactosylceramide alpha-2, 3-sialyltransferase, isoform 5 NP_001341176.1 (SEQ ID NO: 390)

1 mtypegapls dleyysndlf vavlfksvdf nwlqamvkke tlpfwvrlff wkqvaekipl

61 qpkhfrilnp viiketafdi Iqysepqsrf wgrdknvpti gviavvlath Icdevslagf

121 gydlnqprtp Ihyfdsqcma amnfqtmhnv ttetkfllkl vkegvvkdls ggidref

Alpha-N-acetylneuraminide alpha-2 , 8-sialyltrans f erase , isoform 1 NP_003025.1 (SEQ ID NO: 391)

1 mspcgrarrq tsrgamavla wkfprtrlpm gasalcvvvl cwlyifpvyr Ipnekeivqg

61 vlqqgtawrr nqtaarafrk qmedccdpah Ifamtkmnsp mgksmwydge flysftidns

121 tyslfpqatp fqlplkkcav vgnggilkks gcgrqidean fvmrcnlppl sseytkdvgs

181 ksqlvtanps iirqrfqnll wsrktfvdnm kiynhsyiym pafsmktgte pslrvyytls

241 dvganqtvlf anpnflrsig kfwksrgiha krlstglflv saalglceev aiygfwpfsv

301 nmheqpishh yydnvlpfsg fhampeeflq Iwylhkigal rmqldpcedt slqpts

Alpha-N-acetylneuraminide alpha-2, 8-sialyltransferase, isoform 2 NP_001291379.1 (SEQ ID NO: 392)

1 mtgsfythsp Itiqltlssh rcnlpplsse ytkdvgsksq Ivtanpsiir qrfqnllwsr

61 ktfvdnmkiy nhsyiympaf smktgtepsl rvyytlsdvg anqtvlfanp nflrsigkfw

121 ksrgihakrl stglflvsaa Iglceevaiy gfwpfsvnmh eqpishhyyd nvlpfsgfha

181 mpeeflqlwy Ihkigalrmq Idpcedtslq pts

Survivin, isoform 1 NP_001159.2 (SEQ ID NO: 393)

1 mgaptlppaw qpflkdhris tfknwpfleg cactpermae agfihcpten epdlaqcffc

61 fkelegwepd ddpieehkkh ssgcaflsvk kqfeeltlge flkldrerak nkiaketnnk

121 kkefeetaek vrraieqlaa md

Survivin, isoform 2 NP_001012270.1 (SEQ ID NO: 394)

1 mgaptlppaw qpflkdhris tfknwpfleg cactpermae agfihcpten epdlaqcffc

61 fkelegwepd ddpmqrkpti rrknlrklrr kcavpssswl pwieasgrsc Ivpewlhhfq

121 glfpgatslp vgplams

Survivin, isoform 3 NP_001012271.1 (SEQ ID NO: 395)

1 mgaptlppaw qpflkdhris tfknwpfleg cactpermae agfihcpten epdlaqcffc 61 fkelegwepd ddpigpgtva yacntstlgg rggritreeh kkhssgcafl svkkqfeelt 121 Igeflkldre raknkiaket nnkkkefeet aekvrraieq laamd T-box 4, isoform 1 NP_001308049.1 (SEQ ID NO: 396)

1 mlqdkglses eeafrapgpa Igeasaanap epalaapgls gaalgsppgp gadvvaaaaa

61 eqtienikvg lhekelwkkf heagtemiit kagrrmfpsy kvkvtgmnpk tkyillidiv

121 paddhrykfc dnkwmvagka epampgrlyv hpdspatgah wmrqlvsfqk Ikltnnhldp

181 fghiilnsmh kyqprlhivk adennafgsk ntafcthvfp etsfisvtsy qnhkitqlki

241 ennpfakgfr gsddsdlrva rlqskeypvi sksimrqrli spqlsatpdv gpllgthqal

301 qhyqhengah sqlaepqdlp Istfptqrds slfyhclkrr adgtrhldlp ckrsyleaps 361 svgedhyfrs pppydqqmls psycsevtpr eacmysgsgp eiagvsgvdd Ipppplscnm 421 wtsvspytsy svqtmetvpy qpfpthftat tmmprlptls aqssqppgna hf svynqlsq 481 sqvrergpsa sfprerglpq gcerkppsph Inaaneflys qtfslsress Iqyhsgmgtv 541 enwtdg

T-box 4, isoform 2 NP_060958.2 (SEQ ID NO: 397)

1 mlqdkglses eeafrapgpa Igeasaanap epalaapgls gaalgsppgp gadvvaaaaa 61 eqtienikvg lhekelwkkf heagtemiit kagrrmfpsy kvkvtgmnpk tkyillidiv 121 paddhrykfc dnkwmvagka epampgrlyv hpdspatgah wmrqlvsfqk Ikltnnhldp 181 fghiilnsmh kyqprlhivk adennafgsk ntafcthvfp etsfisvtsy qnhkitqlki 241 ennpfakgfr gsddsdlrva rlqskeypvi sksimrqrli spqlsatpdv gpllgthqal 301 qhyqhengah sqlaepqdlp Istfptqrds slfyhclkrr dgtrhldlpc krsyleapss 361 vgedhyfrsp ppydqqmlsp sycsevtpre acmysgsgpe iagvsgvddl ppppls cnmw 421 tsvspytsys vqtmetvpyq pfpthftatt mmprlptlsa qssqppgnah f svynqlsqs 481 qvrergpsas fprerglpqg cerkppsphl naaneflysq tfslsressl qyhsgmgtve 541 nwtdg

Angiopoietin-1 receptor, isoform 1 NP_000450.2 (SEQ ID NO: 398)

1 mdslaslvlc gvslllsgtv egamdlilin slplvsdaet sltciasgwr phepitigrd 61 fealmnqhqd plevtqdvtr ewakkvvwkr ekaskingay fcegrvrgea irirtmkmrq 121 qasflpatlt mtvdkgdnvn isfkkvlike edaviykngs fihsvprhev pdilevhlph 181 aqpqdagvys aryiggnlft saftrlivrr ceaqkwgpec nhlctacmnn gvchedtgec 241 icppgfmgrt cekacelhtf grtckercsg qegcksyvfc Ipdpygcsca tgwkglqcne 301 achpgfygpd cklrcscnng emcdrfqgcl cspgwqglqc eregiprmtp kivdlpdhie 361 vnsgkfnpic kasgwplptn eemtlvkpdg tvlhpkdfnh tdhfsvaift ihrilppdsg 421 vwvcsvntva gmvekpfnis vkvlpkplna pnvidtghnf avinissepy fgdgpikskk 481 llykpvnhye awqhiqvtne ivtlnylepr teyelcvqlv rrgeggeghp gpvrrf ttas 541 iglppprgln llpksqttln Itwqpifpss eddfyvever rsvqksdqqn ikvpgnltsv 601 llnnlhpreq yvvrarvntk aqgewsedlt awtlsdilpp qpenikisni thssaviswt 661 ildgysissi tirykvqgkn edqhvdvkik natitqyqlk glepetayqv di f aennigs 721 snpafshelv tlpesqapad Igggkmllia ilgsagmtcl tvllafliil qlkranvqrr 781 maqafqnvre epavqfnsgt lalnrkvknn pdptiypvld wndikfqdvi gegnfgqvlk 841 arikkdglrm daaikrmkey askddhrdfa gelevlcklg hhpniinllg acehrgylyl 901 aieyaphgnl Idflrksrvl etdpafaian stastlssqq llhfaadvar gmdylsqkqf 961 ihrdlaarni Ivgenyvaki adfglsrgqe vyvkktmgrl pvrwmaiesl nysvyttnsd 1021 vwsygvllwe ivslggtpyc gmtcaelyek Ipqgyrlekp Incddevydl mrqcwrekpy 1081 erpsfaqilv slnrmleerk tyvnttlyek ftyagidcsa eeaa

Angiopoietin-1 receptor, isoform 2 NP_001277006.1 (SEQ ID NO: 399)

1 mdslaslvlc gvslllsgtv egamdlilin slplvsdaet sltciasgwr phepitigrd 61 fealmnqhqd plevtqdvtr ewakkvvwkr ekaskingay fcegrvrgea irirtmkmrq 121 qasflpatlt mtvdkgdnvn isfkkvlike edaviykngs fihsvprhev pdilevhlph 181 aqpqdagvys aryiggnlft saftrlivrr ceaqkwgpec nhlctacmnn gvchedtgec 241 icppgfmgrt cekacelhtf grtckercsg qegcksyvfc Ipdpygcsca tgwkglqcne 301 giprmtpkiv dlpdhievns gkfnpickas gwplptneem tlvkpdgtvl hpkdfnhtdh 361 fsvaiftihr ilppdsgvwv csvntvagmv ekpfnisvkv Ipkplnapnv idtghnfavi 421 nissepyfgd gpikskklly kpvnhyeawq hiqvtneivt Inyleprtey elcvqlvrrg 481 eggeghpgpv rrfttasigl ppprglnllp ksqttlnltw qpifpssedd f yveverrsv 541 qksdqqnikv pgnltsvlln nlhpreqyvv rarvntkaqg ewsedltawt Isdilppqpe 601 nikisniths saviswtild gysissitir ykvqgknedq hvdvkiknat itqyqlkgle 661 petayqvdif aennigssnp afshelvtlp esqapadlgg gkmlliailg sagmtcltvl 721 lafliilqlk ranvqrrmaq afqnvreepa vqfnsgtlal nrkvknnpdp tiypvldwnd 781 ikfqdvigeg nfgqvlkari kkdglrmdaa ikrmkeyask ddhrdfagel evlcklghhp 841 niinllgace hrgylylaie yaphgnlldf Irksrvletd pafaiansta stls sqqllh 901 faadvargmd ylsqkqfihr dlaarnilvg enyvakiadf glsrgqevyv kktmgrlpvr 961 wmaieslnys vyttnsdvws ygvllweivs Iggtpycgmt caelyeklpq gyrlekplnc 1021 ddevydlmrq cwrekpyerp sfaqilvsln rmleerktyv nttlyekfty agidcsaeea 1081 a

Angiopoietin-1 receptor, isoform 3 NP_001277007.1 (SEQ ID NO: 400)

1 mdslaslvlc gvslllsasf Ipatltmtvd kgdnvnisfk kvlikeedav iykngs f ihs 61 vprhevpdil evhlphaqpq dagvysaryi ggnlftsaft rlivrrceaq kwgpecnhlc 121 tacmnngvch edtgecicpp gfmgrtceka celhtfgrtc kercsgqegc ksyvf clpdp 181 ygcscatgwk glqcnegipr mtpkivdlpd hievnsgkfn pickasgwpl ptneemtlvk 241 pdgtvlhpkd fnhtdhfsva iftihrilpp dsgvwvcsvn tvagmvekpf nisvkvlpkp 301 Inapnvidtg hnfaviniss epyfgdgpik skkllykpvn hyeawqhiqv tneivtlnyl

361 eprteyelcv qlvrrgegge ghpgpvrrft tasiglpppr glnllpksqt tlnltwqpif

421 psseddfyve verrsvqksd qqnikvpgnl tsvllnnlhp reqyvvrarv ntkaqgewse

481 dltawtlsdi Ippqpeniki snithssavi swtildgysi ssitirykvq gknedqhvdv

541 kiknatitqy qlkglepeta yqvdifaenn igssnpafsh elvtlpesqa padlgggkml

601 liailgsagm tcltvllafl iilqlkranv qrrmaqafqn reepavqfns gtlalnrkvk

661 nnpdptiypv Idwndikfqd vigegnfgqv Ikarikkdgl rmdaaikrmk eyaskddhrd

721 fagelevlck Ighhpniinl Igacehrgyl ylaieyaphg nlldflrksr vletdpafai

781 anstastlss qqllhfaadv argmdylsqk qfihrdlaar nilvgenyva kiadfglsrg

841 qevyvkktmg rlpvrwmaie slnysvyttn sdvwsygvll weivslggtp ycgmtcaely

901 eklpqgyrle kplncddevy dlmrqcwrek pyerpsfaqi Ivslnrmlee rktyvnttly

961 ekftyagidc saeeaa

Telomerase reverse transcriptase, isoform 1 NP_937983.2 (SEQ ID NO: 401)

1 mpraprcrav rsllrshyre vlplatfvrr Igpqgwrlvq rgdpaafral vaqclvcvpw

61 darpppaaps frqvsclkel varvlqrlce rgaknvlafg falldgargg ppeafttsvr

121 sylpntvtda Irgsgawgll Irrvgddvlv hllarcalfv Ivapscayqv cgpplyqlga

181 atqarpppha sgprrrlgce rawnhsvrea gvplglpapg arrrggsasr slplpkrprr

241 gaapepertp vgqgswahpg rtrgpsdrgf cvvsparpae eatslegals gtrhshpsvg

301 rqhhagppst srpprpwdtp cppvyaetkh flyssgdkeq Irpsfllssl rpsltgarrl

361 vetiflgsrp wmpgtprrlp rlpqrywqmr plflellgnh aqcpygvllk thcplraavt

421 paagvcarek pqgsvaapee edtdprrlvq llrqhsspwq vygfvraclr rlvppglwgs

481 rhnerrflrn tkkfislgkh aklslqeltw kmsvrdcawl rrspgvgcvp aaehrlreei

541 lakflhwlms vyvvellrsf fyvtettfqk nrlffyrksv wsklqsigir qhlkrvqlre

601 Iseaevrqhr earpalltsr Irfipkpdgl rpivnmdyvv gartfrrekr aerltsrvka

661 Ifsvlnyera rrpgllgasv Iglddihraw rtfvlrvraq dpppelyfvk vdvtgaydti

721 pqdrltevia siikpqntyc vrryavvqka ahghvrkafk shvstltdlq pymrqfvahl

781 qetsplrdav vieqssslne assglfdvfl rfmchhavri rgksyvqcqg ipqgsilstl

841 Icslcygdme nklfagirrd glllrlvddf llvtphltha ktflrtlvrg vpeygcvvnl

901 rktvvnfpve dealggtafv qmpahglfpw cgllldtrtl evqsdyssya rtsirasltf

961 nrgfkagrnm rrklfgvlrl kchslfldlq vnslqtvctn iykilllqay rfhacvlqlp

1021 fhqqvwknpt fflrvisdta slcysilkak nagmslgakg aagplpseav qwlchqafll

1081 kltrhrvtyv pllgslrtaq tqlsrklpgt tltaleaaan palpsdfkti Id

Telomerase reverse transcriptase, isoform 2 NP_001180305.1 (SEQ ID NO: 402)

1 mpraprcrav rsllrshyre vlplatfvrr Igpqgwrlvq rgdpaafral vaqclvcvpw

61 darpppaaps frqvsclkel varvlqrlce rgaknvlafg falldgargg ppeafttsvr

121 sylpntvtda Irgsgawgll Irrvgddvlv hllarcalfv Ivapscayqv cgpplyqlga

181 atqarpppha sgprrrlgce rawnhsvrea gvplglpapg arrrggsasr slplpkrprr

241 gaapepertp vgqgswahpg rtrgpsdrgf cvvsparpae eatslegals gtrhshpsvg

301 rqhhagppst srpprpwdtp cppvyaetkh flyssgdkeq Irpsfllssl rpsltgarrl

361 vetiflgsrp wmpgtprrlp rlpqrywqmr plflellgnh aqcpygvllk thcplraavt

421 paagvcarek pqgsvaapee edtdprrlvq llrqhsspwq vygfvraclr rlvppglwgs

481 rhnerrflrn tkkfislgkh aklslqeltw kmsvrdcawl rrspgvgcvp aaehrlreei

541 lakflhwlms vyvvellrsf fyvtettfqk nrlffyrksv wsklqsigir qhlkrvqlre

601 Iseaevrqhr earpalltsr Irfipkpdgl rpivnmdyvv gartfrrekr aerltsrvka

661 Ifsvlnyera rrpgllgasv Iglddihraw rtfvlrvraq dpppelyfvk vdvtgaydti

721 pqdrltevia siikpqntyc vrryavvqka ahghvrkafk shvstltdlq pymrqfvahl

781 qetsplrdav vieqssslne assglfdvfl rfmchhavri rgksyvqcqg ipqgsilstl

841 Icslcygdme nklfagirrd glllrlvddf llvtphltha ktflsyarts irasltfnrg

901 fkagrnmrrk Ifgvlrlkch slfldlqvns Iqtvctniyk illlqayrfh acvlqlpfhq

961 qvwknptffl rvisdtaslc ysilkaknag mslgakgaag plpseavqwl chqafllklt

1021 rhrvtyvpll gslrtaqtql srklpgttlt aleaaanpal psdfktild

Cellular tumor antigen p53, isoform a NP_000537.3, NP_001119584.1 (SEQ ID NO: 403)

1 meepqsdpsv epplsqetfs dlwkllpenn vlsplpsqam ddlmlspddi eqwftedpgp

61 deaprmpeaa ppvapapaap tpaapapaps wplsssvpsq ktyqgsygfr Igflhsgtak

121 svtctyspal nkmfcqlakt cpvqlwvdst pppgtrvram aiykqsqhmt evvrrcphhe

181 rcsdsdglap pqhlirvegn Irveylddrn tfrhsvvvpy eppevgsdct tihynymcns

241 scmggmnrrp iltiitleds sgnllgrnsf evrvcacpgr drrteeenlr kkgephhelp

301 pgstkralpn ntssspqpkk kpldgeyftl qirgrerfem frelnealel kdaqagkepg

361 gsrahsshlk skkgqstsrh kklmfktegp dsd

Cellular tumor antigen p53, isoform b NP_001119586.1 (SEQ ID NO: 404)

1 meepqsdpsv epplsqetfs dlwkllpenn vlsplpsqam ddlmlspddi eqwftedpgp 61 deaprmpeaa ppvapapaap tpaapapaps wplsssvpsq ktyqgsygfr Igflhsgtak

121 svtctyspal nkmfcqlakt cpvqlwvdst pppgtrvram aiykqsqhmt evvrrcphhe

181 rcsdsdglap pqhlirvegn Irveylddrn tfrhsvvvpy eppevgsdct tihynymcns 241 scmggmnrrp iltiitleds sgnllgrnsf evrvcacpgr drrteeenlr kkgephhelp 301 pgstkralpn ntssspqpkk kpldgeyftl qdqtsfqken c Cellular tumor antigen p53, isoform C NP_001119585.1 (SEQ ID NO: 405) 1 meepqsdpsv epplsqetfs dlwkllpenn vlsplpsqam ddlmlspddi eqwf tedpgp 61 deaprmpeaa ppvapapaap tpaapapaps wplsssvpsq ktyqgsygfr Igflhsgtak

121 svtctyspal nkmfcqlakt cpvqlwvdst pppgtrvram aiykqsqhmt evvrrcphhe

181 rcsdsdglap pqhlirvegn Irveylddrn tfrhsvvvpy eppevgsdct tihynymcns

241 scmggmnrrp iltiitleds sgnllgrnsf evrvcacpgr drrteeenlr kkgephhelp

301 pgstkralpn ntssspqpkk kpldgeyftl qmlldlrwcy flinss

Cellular tumor antigen p53j isoform d NP_001119587.1 (SEQ ID NO: 406)

1 mfcqlaktcp vqlwvdstpp pgtrvramai ykqsqhmtev vrrcphherc sdsdglappq

61 hlirvegnlr veylddrntf rhsvvvpyep pevgsdctti hynymcnssc mg gmnrrpil

121 tiitledssg nllgrnsfev rvcacpgrdr rteeenlrkk gephhelppg stkralpnnt 181 ssspqpkkkp Idgeyftlqi rgrerfemfr elnealelkd aqagkepggs rahsshlksk 241 kgqstsrhkk Imfktegpds d Cellular tumor antigen p53j isoform e NP_001119588.1 (SEQ ID NO: 407) 1 mfcqlaktcp vqlwvdstpp pgtrvramai ykqsqhmtev vrrcphherc sdsdglappq 61 hlirvegnlr veylddrntf rhsvvvpyep pevgsdctti hynymcnssc mg gmnrrpil

121 tiitledssg nllgrnsfev rvcacpgrdr rteeenlrkk gephhelppg stkralpnnt

181 ssspqpkkkp Idgeyftlqd qtsfqkenc

Cellular tumor antigen p53j isoform f NP_001119589.1 (SEQ ID NO: 408)

1 mfcqlaktcp vqlwvdstpp pgtrvramai ykqsqhmtev vrrcphherc sdsdglappq

61 hlirvegnlr veylddrntf rhsvvvpyep pevgsdctti hynymcnssc mg gmnrrpil

121 tiitledssg nllgrnsfev rvcacpgrdr rteeenlrkk gephhelppg stkralpnnt

181 ssspqpkkkp Idgeyftlqm lldlrwcyfl inss Cellular tumor antigen p53j isoform g NP-001119590.1, NP_001263689.1 , NP_001263690.1 (SEQ ID NO: 409) 1 mddlmlspdd ieqwftedpg pdeaprmpea appvapapaa ptpaapapap swplsssvps 61 qktyqgsygf rlgflhsgta ksvtctyspa Inkmfcqlak tcpvqlwvds tpppgtrvra

121 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr nt f rhs vvvp

181 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns f evrvcacpg 241 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqirgrer f e 301 mfrelneale Ikdaqagkep ggsrahsshl kskkgqstsr hkklmfkteg pdsd Cellular tumor antigen p53j isoform h NP_001263624.1 (SEQ ID NO: 410) 1 mddlmlspdd ieqwftedpg pdeaprmpea appvapapaa ptpaapapap swplsssvps 61 qktyqgsygf rlgflhsgta ksvtctyspa Inkmfcqlak tcpvqlwvds tpppgtrvra

121 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr nt f rhs vvvp

181 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns f evrvcacpg 241 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqmlldlrwc 301 yflinss Cellular tumor antigen p53j isoform i NP_001263625.1 (SEQ ID NO: 411) 1 mddlmlspdd ieqwftedpg pdeaprmpea appvapapaa ptpaapapap swplsssvps

61 qktyqgsygf rlgflhsgta ksvtctyspa Inkmfcqlak tcpvqlwvds tpppgtrvra

121 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr nt f rhs vvvp 181 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns f evrvcacpg 241 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqdqts f qke 301 nc

Cellular tumor antigen p53j isoform j NP_001263626.1 (SEQ ID NO: 412)

1 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr nt f rhs vvvp

61 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns f evrvcacpg 121 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqirgrer fe 181 mfrelneale Ikdaqagkep ggsrahsshl kskkgqstsr hkklmfkteg pdsd Cellular tumor antigen p53j isoform k NP_001263627.1 (SEQ ID NO: 413) 1 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr nt f rhs vvvp

61 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns f evrvcacpg

121 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqdqts f qke 181 nc

Cellular tumor antigen p53j isoform 1 NP_001263628.1 (SEQ ID NO: 414) 1 maiykqsqhm tevvrrcphh ercsdsdgla ppqhlirveg nlrveylddr ntfrhsvvvp

61 yeppevgsdc ttihynymcn sscmggmnrr piltiitled ssgnllgrns fevrvcacpg

121 rdrrteeenl rkkgephhel ppgstkralp nntssspqpk kkpldgeyft Iqmlldlrwc

181 yflinss

Dopachrome tautomerase, isoform 1 NP_001913.2 (SEQ ID NO: 415)

1 msplwwgfll sclgckilpg aqgqfprvcm tvdslvnkec cprlgaesan vcgsqqgrgq

61 ctevradtrp wsgpyilrnq ddrelwprkf fhrtckctgn fagyncgdck fgwtgpncer

121 kkppvirqni hslspqereq flgaldlakk rvhpdyvitt qhwlgllgpn gtqpqfancs

181 vydffvwlhy ysvrdtllgp grpyraidfs hqgpafvtwh ryhllclerd Iqrlignesf

241 alpywnfatg rnecdvctdq Ifgaarpddp tlisrnsrfs swetvcdsld dynhlvtlcn

301 gtyegllrrn qmgrnsmklp tlkdirdcls Iqkfdnppff qnstfsfrna legfdkadgt

361 Idsqvmslhn Ivhsflngtn alphsaandp ifvvlhsftd aifdewmkrf nppadawpqe

421 lapighnrmy nmvpffppvt neelfltsdq Igysyaidlp vsveetpgwp ttllvvmgtl

481 valvglfvll aflqyrrlrk gytplmethl sskryteea

Dopachrome tautomerase, isoform 2 NP_001123361.1 (SEQ ID NO: 416)

1 msplwwgfll sclgckilpg aqgqfprvcm tvdslvnkec cprlgaesan vcgsqqgrgq

61 ctevradtrp wsgpyilrnq ddrelwprkf fhrtckctgn fagyncgdck fgwtgpncer

121 kkppvirqni hslspqereq flgaldlakk rvhpdyvitt qhwlgllgpn gtqpqfancs

181 vydffvwlhy ysvrdtllgp grpyraidfs hqgpafvtwh ryhllclerd Iqrlignesf

241 alpywnfatg rnecdvctdq Ifgaarpddp tlisrnsrfs swetvcdsld dynhlvtlcn

301 gtyegllrrn qmgrnsmklp tlkdirdcls Iqkfdnppff qnstfsfrna legfdkadgt

361 Idsqvmslhn Ivhsflngtn alphsaandp ifvvisnrll ynattnileh vrkekatkel

421 pslhvlvlhs ftdaifdewm krfnppadaw pqelapighn rmynmvpffp pvtneelflt

481 sdqlgysyai dlpvsveetp gwpttllvvm gtlvalvglf vllaflqyrr Irkgytplme

541 thlsskryte ea

Dopachrome tautomerase, isoform 3 NP_001309111.1, NP_001309112.1, NP_001309113.1, NP_001309114.1 (SEQ ID NO: 417)

1 mgrnsmklpt Ikdirdclsl qkfdnppffq nstfsfrnal egfdkadgtl dsqvmslhnl

61 vhsflngtna Iphsaandpi fvvlhsftda ifdewmkrfn ppadawpqel apighnrmyn

121 mvpffppvtn eelfltsdql gysyaidlpv sveetpgwpt tllvvmgtlv alvglfvlla

181 flqyrrlrkg ytplmethls skryteea

Dopachrome tautomerase, isoform 4, NP_001309115.1 (SEQ ID NO: 418)

1 mllgiqrqmk crlrsdvtkr leedehvnth spmrrgnfag yncgdckfgw tgpncerkkp

61 pvirqnihsl spqereqflg aldlakkrvh pdyvittqhw Igllgpngtq pqfancsvyd

121 ffvwlhyysv rdtllgpgrp yraidfshqg pafvtwhryh llclerdlqr lignesfalp

181 ywnfatgrne cdvctdqlfg aarpddptli srnsrfsswe tvcdslddyn hlvtlcngty

241 egllrrnqmg rnsmklptlk dirdclslqk fdnppffqns tfsfrnaleg fdkadgtlds

301 qvmslhnlvh sflngtnalp hsaandpifv vlhsftdaif dewmkrfnpp adawpqelap

361 ighnrmynmv pffppvtnee Ifltsdqlgy syaidlpvsv eetpgwpttl Ivvmgtlval

421 vglfvllafl qyrrlrkgyt plmethlssk ryteea

Transformation/transcription domain associated protein, isoform 1 NP_001231509.1 (SEQ ID NO: 419)

1 mafvatqgat vvdqttlmkk ylqfvaaltd vntpdetklk mmqevsenfe nvtsspqyst

61 flehiiprfl tflqdgevqf Iqekpaqqlr klvleiihri ptnehlrpht knvlsvmfrf

121 leteneenvl iclriiielh kqfrppitqe ihhfldfvkq iykelpkvvn ryfenpqvip

181 entvpppemv gmittiavkv nperedsetr thsiiprgsl slkvlaelpi ivvlmyqlyk

241 Inihnvvaef vplimntiai qvsaqarqhk lynkelyadf iaaqiktlsf layiiriyqe

301 Ivtkysqqmv kgmlqllsnc paetahlrke lliaakhilt telrnqfipc mdklfdesil

361 igsgytaret Irplaystla dlvhhvrqhl plsdlslavq Ifakniddes Ipssiqtmsc

421 klllnlvdci rskseqesgn grdvlmrmle vfvlkfhtia ryqlsaifkk ckpqselgav

481 eaalpgvpta paapgpapsp apvpappppp pppppatpvt papvppfekq gekdkedkqt

541 fqvtdcrslv ktlvcgvkti twgitsckap geaqfipnkq Iqpketqiyi klvkyamqal

601 diyqvqiagn gqtyirvanc qtvrmkeeke vlehfagvft mmnpltfkei fqttvpymve

661 risknyalqi vansflanpt tsalfatilv eylldrlpem gsnvelsnly Iklfklvfgs

721 vslfaaeneq mlkphlhkiv nssmelaqta kepynyflll ralfrsiggg shdllyqefl

781 pllpnllqgl nmlqsglhkq hmkdlfvelc Itvpvrlssl Ipylpmlmdp Ivsalngsqt

841 Ivsqglrtle Icvdnlqpdf lydhiqpvra elmqalwrtl rnpadsishv ayrvlgkfgg

901 snrkmlkesq klhyvvtevq gpsitvefsd ckaslqlpme kaietaldcl ksantepyyr

961 rqawevikcf Ivammsledn khalyqllah pnftektipn viishrykaq dtparktfeq

1021 altgafmsav ikdlrpsalp fvaslirhyt mvavaqqcgp fllpcyqvgs qpstamfhse

1081 engskgmdpl vlidaiaicm ayeekelcki gevalavifd vasiilgske racqlplfsy 1141 iverlcaccy eqawyaklgg vvsikflmer Ipltwvlqnq qtflkallfv mmdltgevsn 1201 gavamakttl eqllmrcatp Ikdeeraeei vaaqeks f hh vthdlvrevt spnstvrkqa 1261 mhslqvlaqv tgksvtvime phkevlqdmv ppkkhllrhq panaqiglme gntf cttlqp 1321 rlftmdlnvv ehkvfytell nlceaedsal tklpcykslp slvplriaal nalaacnylp 1381 qsrekiiaal fkalnstnse Iqeageacmr kf legatiev dqihthmrpl Immlgdyrsl 1441 tlnvvnrlts vtrlfpnsfn dkfcdqmmqh Irkwmevvvi thkggqrsdg nesisecgrc 1501 plspfcqfee mkicsaiinl fhlipaapqt Ivkpllevvm kteramliea gspf replik 1561 fltrhpsqtv elfmmeatln dpqwsrmfms f Ikhkdarpl rdvlaanpnr f itlllpgga 1621 qtavrpgsps tstmrldlqf qaikiisiiv knddswlasq hslvsqlrrv wvsenf qerh 1681 rkenmaatnw kepkllaycl Inyckrnygd iellf qllra f tgrf lenmt flkeymeeei 1741 pknysiaqkr alffrfvdfn dpnfgdelka kvlqhilnpa f lys f ekgeg eqllgppnpe 1801 gdnpesitsv fitkvldpek qadmldslri yllqyatllv ehaphhihdn nknrnsklrr 1861 Imtfawpcll skacvdpack ysghlllahi iakfaihkki vlqvfhsllk ahamearaiv 1921 rqamailtpa vparmedghq mlthwtrkii veeghtvpql vhilhlivqh f kvyypvrhh 1981 Ivqhmvsamq rlgftpsvti eqrrlavdls evvikwelqr ikdqqpdsdm dpns sgegvn 2041 svsssikrgl svdsaqevkr frtatgaisa vfgrsqslpg adsllakpid kqhtdtvvnf 2101 lirvacqvnd ntntagspge vlsrrcvnll ktalrpdmwp kselklqwfd kllmtveqpn 2161 qvnygnictg levlsflltv Iqspailssf kplqrgiaac mtcgntkvlr avhsllsrlm 2221 sifptepsts svaskyeele clyaavgkvi yegltnyeka tnanpsqlf g tlmilksacs 2281 nnpsyidrli svfmrslqkm vrehlnpqaa sgsteatsgt selvmlslel vktrlavmsm 2341 emrknfiqai Itsliekspd akilravvki veewvknnsp maanqtptlr eksillvkmm 2401 tyiekrfped lelnaqfldl vnyvyrdetl sgseltakle paflsglrca qplirakf fe 2461 vfdnsmkrrv yerllyvtcs qnweamgnhf wikqcielll avcekstpig ts cqgamlps 2521 itnvinlads hdraafamvt hvkqeprere nseskeedve idielapgdq tstpktkels 2581 ekdignqlhm Itnrhdkfld tlrevktgal Isafvqlchi sttlaektwv ql fprlwkil 2641 sdrqqhalag eispflcsgs hqvqrdcqps alncf veams qcvppipirp cvlkylgkth 2701 nlwfrstlml ehqafekgls Iqikpkqtte f yeqesitpp qqeildslae lysllqeedm 2761 waglwqkrck ysetataiay eqhgffeqaq esyekamdka kkehersnas paifpeyqlw 2821 edhwircske Inqwealtey gqskghinpy Ivlecawrvs nwtamkealv qvevscpkem 2881 awkvnmyrgy laichpeeqq Isfierlvem asslairewr rlphvvshvh tpllqaaqqi 2941 ielqeaaqin aglqptnlgr nnslhdmktv vktwrnrlpi vsddlshwss ifmwrqhhyq 3001 gkptwsgmhs ssivtayens sqhdpssnna mlgvhasasa iiqygkiark qglvnvaldi 3061 Isrihtiptv pivdcfqkir qqvkcylqla gvmgknecmq gleviestnl kyftkemtae 3121 fyalkgmfla qinkseeank afsaavqmhd vlvkawamwg dylenifvke rqlhlgvsai 3181 tcylhacrhq nesksrkyla kvlwllsfdd dkntladavd kycigvppiq wlawipqllt 3241 clvgsegkll Inlisqvgrv ypqavyfpir tlyltlkieq reryksdpgp iratapmwrc 3301 srimhmqrel hptllssleg ivdqmvwfre nwheevlrql qqglakcysv af eksgavsd 3361 akitphtlnf vkklvstfgv glenvsnvst mf ssaasesl arraqataqd pvfqklkgqf 3421 ttdfdfsvpg smklhnlisk Ikkwikilea ktkqlpkf f 1 ieekcrf Isn f saqtaevei 3481 pgeflmpkpt hyyikiarfm prveivqkhn taarrlyirg hngkiypylv mndacltesr 3541 reervlqllr llnpclekrk ettkrhlfft vprvvavspq mrlvednps s Islveiykqr 3601 cakkgiehdn pisryydrla tvqargtqas hqvlrdilke vqsnmvprsm Ikewalht fp 3661 natdywtfrk mftiqlalig faefvlhlnr Inpemlqiaq dtgklnvay f rf dindatgd 3721 Idanrpvpfr Itpniseflt tigvsgplta smiavarcfa qpnf kvdgil ktvlrdeiia 3781 whkktqedts splsaagqpe nmdsqqlvsl vqkavtaimt rlhnlaqf eg geskvntlva 3841 aansldnlcr mdpawhpwl

Transformation/transcription domain associated protein, isoform 2 NP_003487.1 (SEQ ID NO: 420)

1 mafvatqgat vvdqttlmkk ylqfvaaltd vntpdetklk mmqevsenf e nvts spqyst 61 flehiiprfl tflqdgevqf Iqekpaqqlr klvleiihri ptnehlrpht knvlsvmf rf 121 leteneenvl iclriiielh kqfrppitqe ihhfldfvkq iykelpkvvn ry f enpqvip 181 entvpppemv gmittiavkv nperedsetr thsiiprgsl slkvlaelpi ivvlmyqlyk 241 Inihnvvaef vplimntiai qvsaqarqhk lynkelyadf iaaqiktls f layiiriyqe 301 Ivtkysqqmv kgmlqllsnc paetahlrke lliaakhilt telrnqf ipc mdklfdesil 361 igsgytaret Irplaystla dlvhhvrqhl plsdlslavq If akniddes Ipssiqtmsc 421 klllnlvdci rskseqesgn grdvlmrmle vfvlkfhtia ryqlsaifkk ckpqselgav 481 eaalpgvpta paapgpapsp apvpappppp pppppatpvt papvppf ekq gekdkedkqt 541 fqvtdcrslv ktlvcgvkti twgitsckap geaqf ipnkq Iqpketqiyi klvkyamqal 601 diyqvqiagn gqtyirvanc qtvrmkeeke vlehf agvf t mmnpltf kei f qttvpymve 661 risknyalqi vansflanpt tsalfatilv eylldrlpem gsnvelsnly Iklfklvfgs 721 vslfaaeneq mlkphlhkiv nssmelaqta kepynyf 111 ralf rsiggg shdllyqefl 781 pllpnllqgl nmlqsglhkq hmkdlfvelc Itvpvrlssl Ipylpmlmdp Ivsalngsqt

841 Ivsqglrtle Icvdnlqpdf lydhiqpvra elmqalwrtl rnpadsishv ayrvlgkf gg

901 snrkmlkesq klhyvvtevq gpsitvefsd ckaslqlpme kaietaldcl ksantepyyr

961 rqawevikcf Ivammsledn khalyqllah pnftektipn viishrykaq dtparktf eq

1021 altgafmsav ikdlrpsalp fvaslirhyt mvavaqqcgp f llpcyqvgs qpstamfhse

1081 engskgmdpl vlidaiaicm ayeekelcki gevalavifd vasiilgske racqlplf sy

1141 iverlcaccy eqawyaklgg vvsikflmer Ipltwvlqnq qtf Ikallfv mmdltgevsn

1201 gavamakttl eqllmrcatp Ikdeeraeei vaaqeksfhh vthdlvrevt spnstvrkqa

1261 mhslqvlaqv tgksvtvime phkevlqdmv ppkkhllrhq panaqiglme gntf cttlqp

1321 rlftmdlnvv ehkvfytell nlceaedsal tklpcykslp slvplriaal nalaacnylp

1381 qsrekiiaal fkalnstnse Iqeageacmr kflegatiev dqihthmrpl Immlgdyrsl

1441 tlnvvnrlts vtrlfpnsfn dkfcdqmmqh Irkwmevvvi thkggqrsdg nemkicsaii

1501 nlfhlipaap qtlvkpllev vmkteramli eagspfrepl ikf Itrhpsq tvel fmmeat

1561 Indpqwsrmf msflkhkdar plrdvlaanp nrfitlllpg gaqtavrpgs pststmrldl

1621 qfqaikiisi ivknddswla sqhslvsqlr rvwvsenfqe rhrkenmaat nwkepkllay

1681 cllnyckrny gdiellfqll raftgrflcn mtflkeymee eipknysiaq kralf f rfvd

1741 fndpnfgdel kakvlqhiln paflysfekg egeqllgppn pegdnpesit svf itkvldp

1801 ekqadmldsl riyllqyatl Ivehaphhih dnnknrnskl rrlmt f awpc llskacvdpa

1861 ckysghllla hiiakfaihk kivlqvfhsl Ikahameara ivrqamailt pavparmedg

1921 hqmlthwtrk iiveeghtvp qlvhilhliv qhfkvyypvr hhlvqhmvsa mqrlgf tpsv

1981 tieqrrlavd Isevvikwel qrikdqqpds dmdpnssgeg vnsvsssikr glsvdsaqev

2041 krfrtatgai savfgrsqsl pgadsllakp idkqhtdtvv nf lirvacqv ndntntagsp

2101 gevlsrrcvn llktalrpdm wpkselklqw fdkllmtveq pnqvnygnic tglevlsfll

2161 tvlqspails sfkplqrgia acmtcgntkv Iravhsllsr Imsifpteps ts svas kyee

2221 leclyaavgk viyegltnye katnanpsql fgtlmilksa csnnpsyidr lisvfmrslq

2281 kmvrehlnpq aasgsteats gtselvmlsl elvktrlavm smemrknfiq ailtslieks

2341 pdakilravv kiveewvknn spmaanqtpt Ireksillvk mmtyiekrfp edlelnaqf 1

2401 dlvnyvyrde tlsgseltak lepaflsglr caqplirakf f evfdnsmkr rvyerllyvt

2461 csqnweamgn hfwikqciel llavcekstp igtscqgaml psitnvinla dshdraaf am

2521 vthvkqepre renseskeed veidielapg dqtstpktke Isekdignql hmltnrhdkf

2581 Idtlrevktg allsafvqlc histtlaekt wvqlfprlwk ilsdrqqhal ageispflcs

2641 gshqvqrdcq psalncfvea msqcvppipi rpcvlkylgk thnlwf rstl mlehqa f ekg

2701 Islqikpkqt tefyeqesit ppqqeildsl aelysllqee dmwaglwqkr ckysetatai

2761 ayeqhgffeq aqesyekamd kakkehersn aspaifpeyq Iwedhwircs kelnqwealt

2821 eygqskghin pylvlecawr vsnwtamkea Ivqvevscpk emawkvnmyr gylaichpee

2881 qqlsfierlv emasslaire wrrlphvvsh vhtpllqaaq qiielqeaaq inaglqptnl

2941 grnnslhdmk tvvktwrnrl pivsddlshw ssifmwrqhh yqaivtayen ssqhdpssnn

3001 amlgvhasas aiiqygkiar kqglvnvald ilsrihtipt vpivdcf qki rqqvkcylql

3061 agvmgknecm qgleviestn Ikyftkemta efyalkgmfl aqinkseean kafsaavqmh

3121 dvlvkawamw gdylenifvk erqlhlgvsa itcylhacrh qnesksrkyl akvlwlls fd

3181 ddkntladav dkycigvppi qwlawipqll tclvgsegkl llnlisqvgr vypqavyfpi

3241 rtlyltlkie qreryksdpg piratapmwr csrimhmqre Ihptlls sle givdqmvwf r

3301 enwheevlrq Iqqglakcys vafeksgavs dakitphtln fvkklvstf g vglenvsnvs

3361 tmfssaases larraqataq dpvfqklkgq fttdfdfsvp gsmklhnlis klkkwikile

3421 aktkqlpkff lieekcrfls nfsaqtaeve ipgeflmpkp thyyikiarf mprveivqkh

3481 ntaarrlyir ghngkiypyl vmndacltes rreervlqll rllnpclekr kettkrhlf f

3541 tvprvvavsp qmrlvednps slslveiykq rcakkgiehd npisryydrl atvqargtqa

3601 shqvlrdilk evqsnmvprs mlkewalhtf pnatdywtfr kmf tiqlali gf aefvlhln

3661 rlnpemlqia qdtgklnvay frfdindatg dldanrpvpf rltpnisef 1 ttigvsgplt

3721 asmiavarcf aqpnfkvdgi Iktvlrdeii awhkktqedt ssplsaagqp enmdsqqlvs

3781 Ivqkavtaim trlhnlaqfe ggeskvntlv aaansldnlc rmdpawhpwl

Tyrosinase precursor NP_000363.1 (SEQ ID NO: 421)

1 mllavlycll wsfqtsaghf pracvssknl mekeccppws gdrspcgqls grgs cqnill

61 snaplgpqfp ftgvddresw psvfynrtcq csgnfmgfnc gnckf gfwgp ncterrllvr 121 rnifdlsape kdkffayltl akhtissdyv ipigtygqmk ngstpmf ndi niydlfvwmh 181 yyvsmdallg gseiwrdidf aheapaflpw hrlfllrweq eiqkltgden f tipywdwrd 241 aekcdictde ymggqhptnp nllspasffs swqivcsrle eynshqslcn gtpegplrrn 301 pgnhdksrtp rlpssadvef clsltqyesg smdkaanfsf rntlegf asp Itgiadasqs 361 smhnalhiym ngtmsqvqgs andpifllhh afvdsifeqw Irrhrplqev ypeanapigh 421 nresymvpfi plyrngdffi sskdlgydys ylqdsdpdsf qdyiksyleq as riwswllg 481 aamvgavlta llaglvsllc rhkrkqlpee kqpllmeked yhslyqshl

Vascular endothelial growth factor A, isoform a NP_001020537.2 (SEQ ID NO: 422)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvyvgar cclmpwslpg

361 phpcgpcser rkhlfvqdpq tckcsckntd srckarqlel nertcrcdkp rr

Vascular endothelial growth factor A, isoform b NP_003367.4 (SEQ ID NO: 423)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvpcgpc serrkhlfvq

361 dpqtckcsck ntdsrckarq lelnertcrc dkprr

Vascular endothelial growth factor A, isoform c NP_001020538.2 (SEQ ID NO: 424)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksrp cgpcserrkh Ifvqdpqtck

361 csckntdsrc karqlelner tcrcdkprr

Vascular endothelial growth factor A, isoform d NP_001020539.2 (SEQ ID NO: 425)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckarqleln

361 ertcrcdkpr r

Vascular endothelial growth factor A, isoform e NP_001020540.2 (SEQ ID NO: 426)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckm

Vascular endothelial growth factor A, isoform f NP_001020541.2 (SEQ ID NO: 427)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe kcdkprr

Vascular endothelial growth factor A, isoform g NP_001028928.1 (SEQ ID NO: 428)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 301 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckarqleln

361 ertcrsltrk d

Vascular endothelial growth factor A, isoform h NP_001165093.1 (SEQ ID NO: 429)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rcdkprr

Vascular endothelial growth factor A, isoform i NP_001165094.1 (SEQ ID NO: 430)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

121 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvyvgar cclmpwslpg

181 phpcgpcser rkhlfvqdpq tckcsckntd srckarqlel nertcrcdkp rr

Vascular endothelial growth factor A, isoform j NP_001165095.1 (SEQ ID NO: 431)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvpcgpc serrkhlfvq 181 dpqtckcsck ntdsrckarq lelnertcrc dkprr

Vascular endothelial growth factor A, isoform k NP_001165096.1 (SEQ ID NO: 432)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksrp cgpcserrkh Ifvqdpqtck 181 csckntdsrc karqlelner tcrcdkprr

Vascular endothelial growth factor A, isoform 1 NP_001165097.1 (SEQ ID NO: 433)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckarqleln 181 ertcrcdkpr r

Vascular endothelial growth factor A, isoform m NP_001165098.1 (SEQ ID NO: 434)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckm

Vascular endothelial growth factor A, isoform n NP_001165099.1 (SEQ ID NO: 435)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe kcdkprr

Vascular endothelial growth factor A, isoform o NP_001165100.1 (SEQ ID NO: 436)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckarqleln 181 ertcrsltrk d

Vascular endothelial growth factor A, isoform p NP_001165101.1 (SEQ ID NO: 437)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rcdkprr

Vascular endothelial growth factor A, isoform q NP_001191313.1 (SEQ ID NO: 438)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd 61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem 121 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvcdkpr r Vascular endothelial growth factor A, isoform r NP_001191314.1 (SEQ ID NO: 439)

1 mtdrqtdtap spsyhllpgr rrtvdaaasr gqgpepapgg gvegvgargv alklfvqllg

61 csrfggavvr ageaepsgaa rsassgreep qpeegeeeee keeergpqwr Igarkpgswt

121 geaavcadsa paarapqala rasgrggrva rrgaeesgpp hspsrrgsas ragpgraset

181 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

241 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

301 sflqhnkcec rpkkdrarqe kksvrgkgkg qkrkrkksry kswsvcdkpr r

Vascular endothelial growth factor A, isoform s NP_001273973.1 (SEQ ID NO: 440)

1 maegggqnhh evvkfmdvyq rsychpietl vdifqeypde ieyifkpscv plmrcggccn 61 deglecvpte esnitmqimr ikphqgqhig emsflqhnkc ecrpkkdrar qenpcgpcse 121 rrkhlfvqdp qtckcscknt dsrckarqle Inertcrcdk prr

Vascular endothelial growth factor A, isoform VEGF-Ax precursor NP_001303939.1 (SEQ ID NO: 441)

1 mnfllswvhw slalllylhh akwsqaapma egggqnhhev vkfmdvyqrs ychpietlvd

61 ifqeypdeie yifkpscvpl mrcggccnde glecvptees nitmqimrik phqgqhigem

121 sflqhnkcec rpkkdrarqe npcgpcserr khlfvqdpqt ckcsckntds rckarqleln 181 ertcrcdkpr rsagqeegas Irvsgtrslt rkd

WD repeat-containing protein 46, isoform 1 NP_005443.3 (SEQ ID NO: 442)

1 metapkpgkd vppkkdklqt krkkprrywe eetvpttaga spgpprnkkn relrpqrpkn

61 ayilkksris kkpqvpkkpr ewknpesqrg Isgtqdpfpg papvpvevvq kfcridksrk

121 Iphskaktrs rlevaeaeee etsikaarse lllaeepgfl egedgedtak icqadiveav

181 diasaakhfd Inlrqfgpyr Inysrtgrhl afggrrghva aldwvtkklm ceinvmeavr

241 dirflhseal lavaqnrwlh iydnqgielh cirrcdrvtr leflpfhfll atasetgflt

301 yldvsvgkiv aalnaragrl dvmsqnpyna vihlghsngt vslwspamke plakilchrg

361 gvravavdst gtymatsgld hqlkifdlrg tyqplstrtl phgaghlafs qrgllvagmg

421 dvvniwagqg kasppsleqp ylthrlsgpv hglqfcpfed vlgvghtggi tsmlvpgage

481 pnfdglesnp yrsrkqrqew evkallekvp aelicldpra laevdvisle qgkkeqierl

541 gydpqakapf qpkpkqkgrs staslvkrkr kvmdeehrdk vrqslqqqhh keakakptga

601 rpsaldrfvr

WD repeat-containing protein 46, isoform 2 NP_001157739.1 (SEQ ID NO: 443)

1 metapkpgkd vppkkdklqt krkkprewkn pesqrglsgt qdpfpgpapv pvevvqkfcr

61 idksrklphs kaktrsrlev aeaeeeetsi kaarsellla eepgfleged gedtakicqa

121 diveavdias aakhfdlnlr qfgpyrlnys rtgrhlafgg rrghvaaldw vtkklmcein

181 vmeavrdirf Ihseallava qnrwlhiydn qgielhcirr cdrvtrlefl pfhfllatas

241 etgfltyldv svgkivaaln aragrldvms qnpynavihl ghsngtvslw spamkeplak

301 ilchrggvra vavdstgtym atsgldhqlk ifdlrgtyqp Istrtlphga ghlafsqrgl

361 Ivagmgdvvn iwagqgkasp psleqpylth rlsgpvhglq fcpfedvlgv ghtggitsml

421 vpgagepnfd glesnpyrsr kqrqewevka llekvpaeli cldpralaev dvisleqgkk

481 eqierlgydp qakapfqpkp kqkgrsstas Ivkrkrkvmd eehrdkvrqs Iqqqhhkeak

541 akptgarpsa Idrfvr

Wilms tumor protein, isoform A NP_000369.4 (SEQ ID NO: 444)

1 mdflllqdpa stcvpepasq htlrsgpgcl qqpeqqgvrd pggiwaklga aeasaerlqg

61 rrsrgasgse pqqmgsdvrd Inallpavps Igggggcalp vsgaaqwapv Idfappgasa

121 ygslggpapp papppppppp phsfikqeps wggaepheeq clsaftvhfs gqftgtagac

181 rygpfgpppp sqassgqarm fpnapylpsc lesqpairnq gystvtfdgt psyghtpshh

241 aaqfpnhsfk hedpmgqqgs Igeqqysvpp pvygchtptd sctgsqalll rtpyssdnly

301 qmtsqlecmt wnqmnlgatl kghstgyesd nhttpilcga qyrihthgvf rgiqdvrrvp

361 gvaptlvrsa setsekrpfm caypgcnkry fklshlqmhs rkhtgekpyq cdfkdcerrf

421 srsdqlkrhq rrhtgvkpfq cktcqrkfsr sdhlkthtrt htgekpfscr wpscqkkfar

481 sdelvrhhnm hqrnmtklql al

Wilms tumor protein, isoform B NP_077742.3 (SEQ ID NO: 445)

1 mdflllqdpa stcvpepasq htlrsgpgcl qqpeqqgvrd pggiwaklga aeasaerlqg

61 rrsrgasgse pqqmgsdvrd Inallpavps Igggggcalp vsgaaqwapv Idfappgasa

121 ygslggpapp papppppppp phsfikqeps wggaepheeq clsaftvhfs gqftgtagac

181 rygpfgpppp sqassgqarm fpnapylpsc lesqpairnq gystvtfdgt psyghtpshh

241 aaqfpnhsfk hedpmgqqgs Igeqqysvpp pvygchtptd sctgsqalll rtpyssdnly

301 qmtsqlecmt wnqmnlgatl kgvaagssss vkwtegqsnh stgyesdnht tpilcgaqyr 361 ihthgvfrgi qdvrrvpgva ptlvrsaset sekrpfmcay pgcnkryfkl shlqmhsrkh 421 tgekpyqcdf kdcerrfsrs dqlkrhqrrh tgvkpfqckt cqrkfsrsdh ikthtrthtg 481 ekpfscrwps cqkkfarsde ivrhhnmhqr nmtklqlal

Wilms tumor protein, isoform D NP_077744.4 (SEQ ID NO: 446)

1 mdflllqdpa stcvpepasq htlrsgpgcl qqpeqqgvrd pggiwaklga aeasaerlqg

61 rrsrgasgse pqqmgsdvrd inallpavps igggggcalp vsgaaqwapv idfappgasa

121 ygslggpapp papppppppp phsfikqeps wggaepheeq clsaftvhfs gqftgtagac

181 rygpfgpppp sqassgqarm fpnapylpsc lesqpairnq gystvtfdgt psyghtpshh

241 aaqfpnhsfk hedpmgqqgs igeqqysvpp pvygchtptd sctgsqalll rtpyssdnly

301 qmtsqlecmt wnqmnlgatl kgvaagssss vkwtegqsnh stgyesdnht tpilcgaqyr

361 ihthgvfrgi qdvrrvpgva ptlvrsaset sekrpfmcay pgcnkryfkl shlqmhsrkh

421 tgekpyqcdf kdcerrfsrs dqlkrhqrrh tgvkpfqckt cqrkfsrsdh Ikthtrthtg

481 ktsekpfscr wpscqkkfar sdelvrhhnm hqrnmtklql al

Wilms tumor protein, isoform E NP_001185480.1 (SEQ ID NO: 447)

1 mekgystvtf dgtpsyghtp shhaaqfpnh sfkhedpmgq qgslgeqqys vpppvygcht

61 ptdsctgsqa lllrtpyssd nlyqmtsqle cmtwnqmnlg atlkgvaags sssvkwtegq

121 snhstgyesd nhttpilcga qyrihthgvf rgiqdvrrvp gvaptlvrsa setsekrpfm

181 caypgcnkry fklshlqmhs rkhtgekpyq cdfkdcerrf srsdqlkrhq rrhtgvkpfq

241 cktcqrkfsr sdhlkthtrt htgekpfscr wpscqkkfar sdelvrhhnm hqrnmtklql

301 al

Wilms tumor protein, isoform F NP_001185481.1 (SEQ ID NO: 448)

1 mekgystvtf dgtpsyghtp shhaaqfpnh sfkhedpmgq qgslgeqqys vpppvygcht

61 ptdsctgsqa lllrtpyssd nlyqmtsqle cmtwnqmnlg atlkghstgy esdnhttpil

121 cgaqyrihth gvfrgiqdvr rvpgvaptlv rsasetsekr pfmcaypgcn kryfklshlq

181 mhsrkhtgek pyqcdfkdce rrfsrsdqlk rhqrrhtgvk pfqcktcqrk fsrsdhlkth

241 trthtgktse kpfscrwpsc qkkfarsdel vrhhnmhqrn mtklqlal

X antigen family member 1, isoform a NP_001091063.2 (SEQ ID NO: 449)

1 mespkkknqq ikvgilhlgs rqkkiriqlr sqcatwkvic kscisqtpgi nldlgsgvkv 61 kiipkeehck mpeageeqpq v

X antigen family member 1, isoform d NP_001091065.1 (SEQ ID NO: 450)

1 mespkkknqq Ikvgilhlgs rqkkiriqlr sqvlgremrd megdlqelhq sntgdksgfg 61 frrqgednt

X-linked inhibitor of apoptosis NP_001158.2, NP_001191330.1 (SEQ ID NO: 451)

1 mtfnsfegsk tcvpadinke eefveefnrl ktfanfpsgs pvsastlara gflytgegdt

61 vrcfschaav drwqygdsav grhrkvspnc rfingfylen satqstnsgi qngqykveny

121 igsrdhfald rpsethadyl irtgqvvdis dtiyprnpam yseearlksf qnwpdyahlt

181 prelasagly ytgigdqvqc fccggklknw epcdrawseh rrhfpncffv igrnlnirse

241 sdavssdrnf pnstnlprnp smadyearif tfgtwiysvn keqlaragfy algegdkvkc

301 fhcgggltdw kpsedpweqh akwypgckyl leqkgqeyin nihlthslee clvrttektp

361 sltrriddti fqnpmvqeai rmgfsfkdik kimeekiqis gsnykslevl vadlvnaqkd

421 smqdessqts iqkeisteeq irrlqeeklc kicmdrniai vfvpcghlvt ckqcaeavdk

481 cpmcytvitf kqkifms

Synthetic peptide (SEQ ID NO: 452)

1 siinfekl

In21 Murine (SEQ ID NO: 453)

1 vfffsgrkcg ctqarpcwap gvwiswv

MMP9 Murine(SEQ ID NO: 454)

1 vfffsgrqmw vytgktvlgp rsldklg EQUIVALENTS

[0398] It is to be understood that while the disclosure has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims:

Claims

CLAIMS We claim:

1. A vaccine for inhibiting or decreasing an immune response in a subject with an autoimmune disease comprising an inhibigen and an effective amount of an adjuvant.

2. The vaccine of claim 1, wherein the inhibigen is a peptide.

3. The vaccine of claim 2, wherein the peptide is encoded by a nucleic acid.

4. The vaccine of claim 3, wherein the nucleic acid is a vector.

5. The vaccine of claim 3, wherein the nucleic acid is an RNA, optionally wherein the

RNA is an mRNA.

6. The vaccine of claim 1, wherein the inhibigen is obtained by a method comprising: a) providing a plurality of bacterial cells or beads, wherein each bacterial cell or bead comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with human antigen presenting cells (APCs); c) contacting the APCs with a plurality of human lymphocytes; e) identifying one or more polypeptides that inhibit and/or suppress cytolytic T cell activity; and f) selecting one or more inhibitory polypeptides; thereby selecting the inhibigen.

7. The vaccine of claim 6, wherein the method further comprises contacting the APCs with the adjuvant.

8. A method of attenuating or decreasing and immune response in a subject with an autoimmune disease, comprising: administering to the subject the vaccine of any one of claims 1-7.

9. The method of claim 8, wherein the administration of the vaccine results in a decreased IFNv cytokine production by the immune cells of the subject.

10. The method of claim 8, wherein the vaccine reduces or abolishes cytolytic T cell activity.

11. The method of claim 8, wherein the autoimmune disease is multiple sclerosis.

12. A method of inhibiting or decreasing an immune response in a subject, the method comprising: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises human antigen presenting cells (APCs) that internalize the bacterial cells or beads; c) contacting the first plurality of human cells with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a heterologous polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on a level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen;

1) selecting as one or more inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; and g) administering to the subject an immunogenic composition comprising one or more of the selected antigens or immunogenic fragment thereof, thereby inhibiting or decreasing, relative to a control, an immune response in the subject.

13. The method of claim 12, wherein the first and second plurality of human cells come from the same donor.

14. The method of claim 13, wherein the donor is the subject.

15. The method of claim 12, wherein the first and second plurality of human cells come from different donors.

16. The method of claim 15, wherein at least one donor is the subject.

17. The method of claim 12, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

18. The method of any one of claims 12-17, wherein the subject is susceptible to or is suffering from an autoimmune disease or overactive immune condition.

19. A method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises human antigen presenting cells (APCs) that internalize the bacterial cells or beads; c) contacting the first plurality of human cells with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a heterologous polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on a level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen;

1) selecting as one or more inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; and g) administering to the subject an immunogenic composition comprising one or more of the selected antigens or immunogenic fragments thereof, thereby treating the autoimmune disease or overactive immune condition.

20. The method of claim 19, wherein the first and second plurality of human cells come from the same donor.

21. The method of claim 20, wherein the donor is the subject.

22. The method of claim 19, wherein the first and second plurality of human cells come from different donors.

23. The method of claim 22, wherein at least one donor is the subject.

24. The method of claim 19, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

25. A method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; restimulating the expanded, selectively stimulated lymphocytes with the plurality of overlapping peptides; and administering the expanded, selectively stimulated lymphocytes (e.g., T cells) to the subject, thereby treating the autoimmune disease or overactive immune condition.

26. The method of claim 25, wherein the first and second plurality of human cells come from the same donor.

27. The method of claim 26, wherein the donor is the subject.

28. The method of claim 25, wherein the first and second plurality of human cells come from different donors.

29. The method of claim 28, wherein at least one donor is the subject.

30. The method of claim 25, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

31. The method of claim 30, wherein the one or more additional donors are susceptible to or are suffering from an autoimmune disease or overactive immune condition.

32. The method of any one of claims 25-31, wherein the method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers.

33. The method of claim any one of claims 25-32, wherein the method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

34. A method of treating a subject susceptible to or suffering from an autoimmune disease or overactive immune condition, the method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; and administering the expanded, selectively stimulated lymphocytes (e.g., T cells) to the subject, thereby treating the autoimmune disease or overactive immune condition.

35. The method of claim 34, wherein the first and second plurality of human cells come from the same donor.

36. The method of claim 35, wherein the donor is the subject.

37. The method of claim 34, wherein the first and second plurality of human cells come from different donors.

38. The method of claim 37, wherein at least one donor is the subject.

39. The method of claim 34, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

40. The method of claim 39, wherein the one or more additional donors are susceptible to or are suffering from an autoimmune disease or overactive immune condition.

41. The method of any one of claims 34-40, wherein the method does not comprise a further step of restimulating the selectively stimulated lymphocytes (e.g., by the one or more of the overlapping peptides).

42. The method of any one of claim 34-41, wherein the method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers.

43. The method of any one of claims 34-42, wherein the method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

44. A pharmaceutical composition comprising a plurality of selectively stimulated lymphocytes, wherein the selectively stimulated lymphocytes are obtained by a method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; restimulating the expanded, selectively stimulated lymphocytes with the plurality of overlapping peptides; and formulating the restimulated, expanded, selectively stimulated lymphocytes (e.g., T cells) from the subject as a pharmaceutical composition.

45. The composition of claim 44, wherein the first and second plurality of human cells come from the same donor.

46. The composition of claim 45, wherein the donor is the subject.

47. The composition of claim 44, wherein the first and second plurality of human cells come from different donors.

48. The composition of claim 47, wherein at least one donor is the subject.

49. The composition of claim 44, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

50. The composition of any one of claims 44-49, wherein the selectively stimulated lymphocytes are obtained by a method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers.

51. The composition of any one of claims 44-50, wherein the selectively stimulated lymphocytes are obtained by a method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

52. A pharmaceutical composition comprising a plurality of selectively stimulated lymphocytes, wherein the selectively stimulated lymphocytes are obtained by a method comprising: selecting one or more antigens by: a) obtaining, providing, or generating a library comprising bacterial cells or beads, wherein each bacterial cell or bead of the library comprises a different heterologous polypeptide; b) contacting the bacterial cells or beads with a first plurality of human cells which comprises antigen presenting cells (APCs), wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with a second plurality of human cells which comprises human lymphocytes, under conditions suitable for activation of lymphocytes by a polypeptide presented by the first plurality of human cells; d) determining whether one or more lymphocytes of the second plurality of human cells are activated by, or not responsive to, one or more polypeptides presented by the first plurality of human cells, e.g., by assessing (e.g., detecting or measuring) a level (e.g., an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more polypeptides that stimulate, inhibit and/or suppress, and/or have a minimal effect on level of expression and/or secretion of one or more immune mediators, wherein stimulation, inhibition and/or suppression indicate that the polypeptide is an antigen; and f) selecting as inhibitory antigens, from among the identified antigens, one or more antigens that (i) inhibit and/or suppress level of expression and/or secretion of one or more immune mediators that increase immune response, and/or that (ii) increase level of expression and/or secretion of one or more immune mediators that decrease immune response; obtaining a sample of PBMCs from the subject; isolating from the sample of PBMCs a population of lymphocytes (e.g., T cells) and a population of CD 14+ monocytes; differentiating the monocytes into dendritic cells; co-culturing the dendritic cells with (i) the population of lymphocytes (e.g., T cells) from the subject, and (ii) a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more of the selected antigens, thereby selectively stimulating the subject’s lymphocytes; expanding, in the presence of one or more cytokines, a plurality of the subject’s lymphocytes (e.g., T cells) selectively stimulated by the one or more selected antigens; and formulating the expanded, selectively stimulated lymphocytes (e.g., T cells) as a pharmaceutical composition.

53. The composition of claim 52, wherein the first and second plurality of human cells come from the same donor.

54. The composition of claim 53, wherein the donor is the subject.

55. The composition of claim 52, wherein the first and second plurality of human cells come from different donors.

56. The composition of claim 55, wherein at least one donor is the subject.

57. The composition of claim 52, wherein steps (b) to (e) are repeated with human cells isolated from one or more additional donors.

58. The composition of any one of claims 52-57, wherein the selectively stimulated lymphocytes are obtained by a method does not comprise a further step of restimulating the selectively stimulated lymphocytes (e.g., by the one or more of the overlapping peptides).

59. The composition of any one of claims 52-58, wherein the selectively stimulated lymphocytes are obtained by a method does not comprise a further step of sorting the lymphocytes (e.g., T cells) by e.g., expression of one or more cell surface markers.

60. The composition of any one of claims 52-59, wherein the selectively stimulated lymphocytes are obtained by a method does not comprise a further step of expanding the lymphocytes (e.g., T cells).

61. The method of any one of claims 12-43, wherein the heterologous polypeptides are derived from a cancer or tumor cell, and the antigens selected are tumor antigens.

62. The method of claim 61, wherein the tumor antigens comprise full-length polypeptides encoding mutations, splice variants, or translocations present in a cancer or tumor.

63. The method of claim 61 or 62, wherein the tumor antigens comprise polypeptides that are fragments of full-length polypeptides encoding mutations, splice variants, or translocations present in a cancer or tumor.

64. The method of any one of claims 12-43, wherein the heterologous polypeptides are derived from a human cell or tissue that is a target of an autoimmune response, and the antigens selected are autoimmune antigens.

65. The method of any one of claims 12-43, wherein the heterologous polypeptides are derived from a healthy human cell or tissue.

66. The method of any one of claims 12-43, wherein the antigens selected are autoantigens.

67. The method of any one of claims 12-43, wherein the heterologous polypeptides are derived from an infectious agent, and the antigens selected are antigens of the infectious agent.

68. The method of any one of claims 12-43 or 61-67, wherein the selected inhibitory antigens comprise a plurality of overlapping peptides, wherein the overlapping peptides comprise all or part of the amino acid sequence of one or more inhibitory antigens.

69. The method of any one of claims 12-43 or 61-68, wherein the library of different heterologous polypeptides comprises at least 1, 3, 5, 10, 15, 20, 25, 30, 50, 100, 150, 250, 500, 750, 1000 or more different heterologous polypeptides, or portions thereof.

70. The method of any one of claims 12-43 or 61-69, wherein determining whether one or more lymphocytes are inhibited and/or suppressed by one or more antigens comprises measuring a level of one or more immune mediators.

71. The method of any one of claims 12-43 or 61-70, wherein the one or more immune mediators are selected from the group consisting of cytokines, soluble mediators, and cell surface markers expressed by the lymphocytes.

72. The method of any one of claims 12-43 or 61-71, wherein the one or more immune mediators are cytokines.

73. The method of claim 72, wherein the one or more cytokines are selected from the group consisting of TRAIL, IFN-gamma, IL-12p70, IL-2, TNF-alpha, MIPl-alpha, MIP1- beta, CXCL9, CXCL10, MCP1, RANTES, IL-1 beta, IL-4, IL-6, IL-8, IL-9, IL-10, IL-13, IL-15, CXCL11, IL-3, IL-5, IL-17, IL-18, IL-21, IL-22, IL-23A, IL-24, IL-27, IL-31, IL-32, TGF-beta, CSF, GM-CSF, TRANCE (also known as RANK L), MIP3-alpha, and fractalkine.

74. The method of any one of claims 12-43 or 61-72, wherein the one or more immune mediators are soluble mediators.

75. The method of claim 74, wherein the one or more soluble mediators are selected from the group consisting of granzyme A, granzyme B, sFas, sFasL, perforin, and granulysin.

76. The method of any one of claims 12-43 or 61-71, wherein the one or more immune mediators are cell surface markers.

77. The method of claim 76, wherein the one or more cell surface markers are selected from the group consisting of CD107a, CD107b, CD25, CD69, CD45RA, CD45RO, CD137 (4-1BB), CD44, CD62L, CD27, CCR7, CD154 (CD40L), KLRG-1, CD71, HLA-DR, CD122 (IL-2RB), CD28, IL7Ra (CD 127), CD38, CD26, CD 134 (OX-40), CTLA-4 (CD 152), LAG- 3, TIM-3 (CD366), CD39, PD1 (CD279), FoxP3, TIGIT, CD160, BTLA, 2B4 (CD244), and KLRG1.

78. The method of any one of claims 12-43 or 61-77, wherein the lymphocytes comprise

CD4+ T cells.

79. The method of any one of claims 12-43 or 61-77, wherein the lymphocytes comprise CD8+ T cells.

80. The method of any one of claims 12-43 or 61-79, wherein lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 20%, 40%, 60%, 80%, 100%, 120%, 140%, 160%, 180%, or 200% higher or lower than a control level.

81. The method of any one of claims 12-43 or 61-79, wherein lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 1, 2, or 3 standard deviations greater or lower than the mean of a control level.

82. The method of any one of claims 12-43 or 61-79, wherein lymphocyte inhibition and/or suppression is determined by assessing a level of one or more expressed or secreted immune mediators that is at least 1, 2, 3, 4 or 5 median absolute deviations (MADs) greater or lower than a median response level to a control.

83. The method of any one of claims 7-32 or 61-82, wherein the autoimmune disease comprises an inflammatory autoimmune disease or disorder associated with an arthritis condition, a multiple sclerosis condition, a diabetic condition, an intestinal inflammatory condition, vasculitis, asthma, or transplant rejection or graft versus host disease.

84. The method of any one of claims 7-32 or 61-83, further comprising administering to the subject a second therapy or combination of therapies for treatment of the autoimmune disease or overactive immune condition.

The method of any one of claims 12-43 or 61-83, wherein the immune response inhibited or decreased comprises a humoral response and/or a cellular response.

85. The method of any one of claims 12-43 or 61-84, wherein the selected inhibitory antigens comprise (i) an antigen described herein (e.g., comprising an amino acid sequence described herein), (ii) a polypeptide having an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence of an antigen described herein, and/or (iii) a polypeptide comprising the amino acid sequence of an antigen described herein having at least one deletion, insertion, and/or translocation.

86. The method of any one of claim 12-43 or 61-85, wherein the immunogenic composition administered to the subject decreases markers of inflammation, T cell activation aberrantly directed to autoantigens, and/or cytotoxicity in a lymphocyte from the subject.

87. The method of any one of claim 12-43 or 61-86, wherein the immunogenic composition administered to the subject decreases expression of markers associated with inflammation, T cell activation aberrantly directed to autoantigens, and/or cytotoxicity in a lymphocyte from the subject.

88. The method of any one of claims 12-43 or 61-87, wherein the immunogenic composition administered to the subject decreases IFNy secretion in a lymphocyte from the subject.

89. The method of any one of claim 12-43 or 61-88, wherein the immunogenic composition administered to the subject decreases T cell receptor expression in a lymphocyte from the subject.

90. The method of any one of claims 12-43 or 61-89, wherein the immunogenic composition administered to the subject increases markers associated with dampening of immune responses or T cell exhaustion.

91. The method of any one of claims 12-43 or 61-90, wherein the immunogenic composition administered to the subject increases expression of markers associated with dampening of immune responses or T cell exhaustion.

92. The method of claim 91, wherein the markers associated with dampening of immune responses or T cell exhaustion comprise PD1, LAG-3, TIM-3, CD43, CD44, CD69, CD160, BLIMP- 1, CTLA-4, 2B4/CD244/SLAMF4, or TIGIT.