Table 3. Differentiation antigens

^aClass II HLA are indicated in blue.
^bFrequency in Caucasians, based on (1) Marsh SGE, Parham P, Barber LD. The HLA Factsbook (Academic Press, 2000) for HLA-A, B, C, and DR, and (2) Colombani J. HLA, Fonctions immunitaires et applications médicales (John Libbey Eurotext, 1993) for HLA-DP and DR.
^cNot available.
^dDifferent alleles encoding tyrosinase have been described. In 50% of Caucasians, the serine residue of nonapeptide SEIWRDIDF is replaced by a tyrosine.
^eThe peptide is composed of two non-contiguous fragments that are spliced by the proteasome.

References

Alves PM, Viatte S, Fagerberg T, Michielin O, Bricard G, Bouzourene H, Vuilleumier H, Kruger T, Givel JC, Lévy F, Speiser DE, Cerottini JC, Romero P. Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients. Cancer Immunol Immunother 2007; 56: 1795-805. (PMID: 17447064)

Bakker AB, Schreurs MW, Tafazzul G, de Boer AJ, Kawakami Y, Adema GJ, Figdor CG. Identification of a novel peptide derived from the melanocyte-specific gp100 antigen as the dominant epitope recognized by an HLA-A2.1-restricted anti-melanoma CTL line. Int J Cancer 1995; 62: 97-102. (PMID: 7541395)

Benlalam H, Linard B, Guilloux Y, Moreau-Aubry A, Derré L, Diez E, Dreno B, Jotereau F, Labarrière N. Identification of five new HLA-B*3501-restricted epitopes derived from common melanoma-associated antigens, spontaneously recognized by tumor-infiltrating lymphocytes. J Immunol 2003; 171: 6283-9. (PMID: 14634146)

Bioley G, Jandus C, Tuyaerts S, Rimoldi D, Kwok WW, Speiser DE, Tiercy JM, Thielemans K, Cerottini JC, Romero P. Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers. J Immunol 2006; 177: 6769-79. (PMID: 17082590)

Brichard VG, Herman J, Van Pel A, Wildmann C, Gaugler B, Wolfel T, Boon T, Lethe B. A tyrosinase nonapeptide presented by HLA-B44 is recognized on a human melanoma by autologous cytolytic T lymphocytes. Eur J Immunol 1996; 26: 224-230. (PMID: 8566071)

Campi G, Crosti M, Consogno G, Facchinetti V, Conti-Fine BM, Longhi R, Casorati G, Dellabona P, Protti MP. CD4+ T cells from healthy subjects and colon cancer patients recognize a carcinoembryonic antigen-specific immunodominant epitope. Cancer Res 2003; 63: 8481-6. (PMID: 14679013)

Castelli C, Storkus WJ, Maeurer MJ, Martin DM, Huang EC, Pramanik BN, Nagabhushan TL, Parmiani G, Lotze MT. Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes. J Exp Med 1995; 181: 363-368. (PMID: 7807017)

Castelli C, Tarsini P, Mazzocchi A, Rini F, Rivoltini L, Ravagnani F, Gallino F, Belli F, Parmiani G. Novel HLA-Cw8-restricted T-cell epitopes derived from tyrosinase-related protein-2 and gp100 melanoma antigens. J Immunol 1999; 162: 1739-1748. (PMID: 9973437)

Correale P, Walmsley K, Nieroda C, Zaremba S, Zhu M, Schlom J, Tsang KY. In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst 1997; 89: 293-300. (PMID: 9048833)

Cox AL, Skipper J, Chen Y, Henderson RA, Darrow TL, Shabanowitz J, Engelhard VH, Hunt DF, Slingluff CL. Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 1994; 264: 716-719. (PMID: 7513441)

Crosti M, Longhi R, Consogno G, Melloni G, Zannini P, Protti MP. Identification of novel subdominant epitopes on the carcinoembryonic antigen recognized by CD4+ T cells of lung cancer patients. J Immunol 2006; 176: 5093-9. (PMID: 16585607)

Godefroy E, Scotto L, Souleimanian NE, Ritter G, Old LJ, Jotereau F, Valmori D, Ayyoub M. Identification of two Melan-A CD4+ T cell epitopes presented by frequently expressed MHC class II alleles. Clin Immunol 2006; 121: 54-62. (PMID: 16814609)

Hural JA, Friedman RS, McNabb A, Steen SS, Henderson RA, Kalos M. Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. J Immunol 2002; 169: 557-65. (PMID: 12077288)

Jaramillo A, Majumder K, Manna PP, Fleming TP, Doherty G, Dipersio JF, Mohanakumar T. Identification of HLA-A3-restricted CD8+ T cell epitopes derived from mammaglobin-A, a tumor-associated antigen of human breast cancer. Int J Cancer 2002; 102: 499-506. (PMID: 12432553)

Kang X, Kawakami Y, el-Gamil M, Wang R, Sakaguchi K, Yannelli JR, Appella E, Rosenberg SA, Robbins PF. Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. J Immunol 1995; 155: 1343-1348. (PMID: 7543520)

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 1994a; 91: 6458-6462. (PMID: 8022805)

Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med 1994b; 180: 347-352. (PMID: 7516411)

Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins PF, Sette A, Appella E, Rosenberg SA. Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol 1995; 154: 3961-3968. (PMID: 7706734)

Kawakami Y, Robbins PF, Wang X, Tupesis JP, Parkhurst MR, Kang X, Sakaguchi K, Appella E, Rosenberg SA. Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles. J Immunol 1998; 161: 6985-6992. (PMID: 9862734)

Kawashima I, Hudson SJ, Tsai V, Southwood S, Takesako K, Appella E, Sette A, Celis E. The multi-epitope approach for immunotherapy for cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol 1998a; 59: 1-14. (PMID: 9544234)

Kawashima I, Tsai V, Southwood S, Takesako K, Celis E, Sette A. Identification of gp100-derived, melanoma-specific cytotoxic T-lymphocyte epitopes restricted by HLA-A3 supertype molecules by primary in vitro immunization with peptide-pulsed dendritic cells. Int J Cancer 1998b; 78: 518-24. (PMID: 9797143)

Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E. Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res 1999; 59: 431-5. (PMID: 9927058)

Kittlesen DJ, Thompson LW, Gulden PH, Skipper JC, Colella TA, Shabanowitz J, Hunt DF, Engelhard VH, Slingluff CL, Shabanowitz JA. Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development. J Immunol 1998; 160: 2099-2106. (PMID: 9498746)

Kobayashi H, Kokubo T, Sato K, Kimura S, Asano K, Takahashi H, Iizuka H, Miyokawa N, Katagiri M. CD4+ T cells from peripheral blood of a melanoma patient recognize peptides derived from nonmutated tyrosinase. Cancer Res 1998; 58: 296-301. (PMID: 9443408)

Kobayashi H, Lu J, Celis E. Identification of helper T-cell epitopes that encompass or lie proximal to cytotoxic T-cell epitopes in the gp100 melanoma tumor antigen. Cancer Res 2001; 61: 7577-84. (PMID: 11606397)

Kobayashi H, Omiya R, Ruiz M, Huarte E, Sarobe P, Lasarte JJ, Herraiz M, Sangro B, Prieto J, Borras-Cuesta F, Celis E. Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen. Clin Cancer Res 2002; 8: 3219-25. (PMID: 12374692)

Lapointe R, Royal RE, Reeves ME, Altomare I, Robbins PF, Hwu P. Retrovirally transduced human dendritic cells can generate T cells recognizing multiple MHC class I and class II epitopes from the melanoma antigen glycoprotein 100. J Immunol 2001; 167: 4758-64. (PMID: 11591807)

Larrieu P, Renaud V, Godet Y, Jotereau F, Fonteneau JF. A HLA-Cw*0701 restricted Melan-A/MART1 epitope presented by melanoma tumor cells to CD8+ tumor infiltrating lymphocytes. Cancer Immunol Immunother 2008; 57: 745-52. (PMID: 18097665)

Lennerz V, Fatho M, Gentilini C, Frye RA, Lifke A, Ferel D, Wölfel C, Huber C, Wölfel T. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci U S A 2005; 102: 16013-8. (PMID: 16247014)

Morel S, Ooms A, Van Pel A, Wolfel T, Brichard VG, van der Bruggen P, Van den Eynde BJ, Degiovanni G. A tyrosinase peptide presented by HLA-B35 is recognized on a human melanoma by autologous cytotoxic T lymphocytes. Int J Cancer 1999; 83: 755-759. (PMID: 10597191)

Noppen C, Lévy F, Burri L, Zajac P, Remmel E, Schaefer C, Lüscher U, Heberer M, Spagnoli GC. Naturally processed and concealed HLA-A2.1-restricted epitopes from tumor-associated antigen tyrosinase-related protein-2. Int J Cancer 2000; 87: 241-6. (PMID: 10861482)

Nukaya I, Yasumoto M, Iwasaki T, Ideno M, Sette A, Celis E, Takesako K, Kato I. Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte. Int J Cancer 1999; 80: 92-7. (PMID: 9935237)

Parkhurst MR, Fitzgerald EB, Southwood S, Sette A, Rosenberg SA, Kawakami Y. Identification of a shared HLA-A*0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2). Cancer Res 1998; 58: 4895-4901. (PMID: 9809996)

Parkhurst MR, Riley JP, Robbins PF, Rosenberg SA. Induction of CD4+ Th1 lymphocytes that recognize known and novel class II MHC restricted epitopes from the melanoma antigen gp100 by stimulation with recombinant protein. J Immunother 2004; 27: 79-91. (PMID: 14770079)

Paschen A, Song M, Osen W, Nguyen XD, Mueller-Berghaus J, Fink D, Daniel N, Donzeau M, Nagel W, Kropshofer H, Schadendorf D. Detection of spontaneous CD4+ T-cell responses in melanoma patients against a tyrosinase-related protein-2-derived epitope identified in HLA-DRB1*0301 transgenic mice. Clin Cancer Res 2005; 11: 5241-7. (PMID: 16033842)

Riley JP, Rosenberg SA, Parkhurst MR. Identification of a new shared HLA-A2.1 restricted epitope from the melanoma antigen tyrosinase. J Immunother 2001; 24: 212-20. (PMID: 11394498)

Robbins PF, El-Gamil M, Li YF, Fitzgerald EB, Kawakami Y, Rosenberg SA. The intronic region of an incompletely spliced gp100 gene transcript encodes an epitope recognized by melanoma-reactive tumor-infiltrating lymphocytes. J Immunol 1997; 159: 303-308. (PMID: 9200467)

Robbins PF, El-Gamil M, Li YF, Zeng G, Dudley M, Rosenberg SA. Multiple HLA class II-restricted melanocyte differentiation antigens are recognized by tumor-infiltrating lymphocytes from a patient with melanoma. J Immunol 2002; 169: 6036-47. (PMID: 12421991)

Ruiz M, Kobayashi H, Lasarte JJ, Prieto J, Borras-Cuesta F, Celis E, Sarobe P. Identification and characterization of a T-helper peptide from carcinoembryonic antigen. Clin Cancer Res 2004; 10: 2860-7. (PMID: 15102695)

Schneider J, Brichard V, Boon T, Meyer zum Buschenfelde KH, Wolfel T. Overlapping peptides of melanocyte differentiation antigen Melan-A/MART-1 recognized by autologous cytolytic T lymphocytes in association with HLA-B45.1 and HLA-A2.1. Int J Cancer 1998; 75: 451-458. (PMID: 9455808)

Sensi M, Pellegatta S, Vegetti C, Nicolini G, Parmiani G, Anichini A. Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones. Tissue Antigens 2002; 59: 273-9. (PMID: 12135425)

Shen L, Schroers R, Hammer J, Huang XF, Chen S-Y. Identification of a MHC class-II restricted epitope in carcinoembryonic antigen. Cancer Immunol Immunother 2004; 53: 391-403. (PMID: 14624313)

Skipper JC, Kittlesen DJ, Hendrickson RC, Deacon DD, Harthun NL, Wagner SN, Hunt DF, Engelhard VH, Slingluff CL. Shared epitopes for HLA-A3-restricted melanoma-reactive human CTL include a naturally processed epitope from Pmel-17/gp100. J Immunol 1996a; 157: 5027-5033. (PMID: 8943411)

Skipper JC, Hendrickson RC, Gulden PH, Brichard V, Van Pel A, Chen Y, Shabanowitz J, Wolfel T, Slingluff CL, Boon T, Hunt DF, Engelhard VH. An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins. J Exp Med 1996b; 183: 527-534. (PMID: 8627164)

Topalian SL, Gonzales MI, Parkhurst M, Li YF, Southwood S, Sette A, Rosenberg SA, Robbins PF. Melanoma-specific CD4+T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med 1996; 183: 1965-1971. (PMID: 8642306)

Touloukian CE, Leitner WW, Topalian SL, Li YF, Robbins PF, Rosenberg SA, Restifo NP. Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. J Immunol 2000; 164: 3535-42. (PMID: 10725708)

Touloukian CE, Leitner WW, Robbins PF, Li YF, Kang X, Lapointe R, Hwu P, Rosenberg SA, Restifo NP. Expression of a "self-"antigen by human tumor cells enhances tumor antigen-specific CD4+ T-cell function. Cancer Res 2002; 62: 5144-7. (PMID: 12234976)

Touloukian CE, Leitner WW, Schnur RE, Robbins PF, Li Y, Southwood S, Sette A, Rosenberg SA, Restifo NP. Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. J Immunol 2003; 170: 1579-85. (PMID: 12538723)

Tsai V, Southwood S, Sidney J, Sakaguchi K, Kawakami Y, Appella E, Sette A, Celis E. Identification of subdominant CTL epitopes of the GP100 melanoma-associated tumor antigen by primary in vitro immunization with peptide-pulsed dendritic cells. J Immunol 1997; 158: 1796-1802. (PMID: 9029118)

Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 1995; 87: 982-990. (PMID: 7629885)

Vigneron N, Stroobant V, Chapiro J, Ooms A, Degiovanni G, Morel S, van der Bruggen P, Boon T, Van den Eynde BJ. An antigenic peptide produced by peptide splicing in the proteasome. Science 2004; 304: 587-90. (PMID: 15001714)

Vigneron N, Ooms A, Morel S, Ma W, Degiovanni G, Van den Eynde BJ. A peptide derived from melanocytic protein gp100 and presented by HLA-B35 is recognized by autologous cytolytic T lymphocytes on melanoma cells. Tissue Antigens 2005; 65: 156-62. (PMID: 15713214)

Walton SM, Gerlinger M, de la Rosa O, Nuber N, Knights A, Gati A, Laumer M, Strauss L, Exner C, Schäfer N, Urosevic M, Dummer R, Tiercy JM, Mackensen A, Jaeger E, Lévy F, Knuth A, Jäger D, Zippelius A. Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients. J Immunol 2006; 177: 8212-8. (PMID: 17114498)

Wang RF, Parkhurst MR, Kawakami Y, Robbins PF, Rosenberg SA. Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen. J Exp Med 1996a; 183: 1131-1140. (PMID: 8642255)

Wang RF, Appella E, Kawakami Y, Kang X, Rosenberg SA. Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes. J Exp Med 1996b; 184: 2207-2216. (PMID: 8976176)

Wang RF, Johnston SL, Southwood S, Sette A, Rosenberg SA. Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33. J Immunol 1998; 160: 890-7. (PMID: 9551926)

Wang W, Epler J, Salazar LG, Riddell SR. Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1. Cancer Res 2006; 66: 6826-33. (PMID: 16818660)

Wolfel T, Van Pel A, Brichard V, Schneider J, Seliger B, Meyer zum Buschenfelde KH, Boon T. Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 1994; 24: 759-764. (PMID: 8125142)

Zarour HM, Kirkwood JM, Salvucci Kierstead L, Herr W, Brusic V, Slingluff CL, Jr., Sidney J, Sette A, Storkus WJ. Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4+ T cells. Proc Natl Acad Sci USA 2000; 97: 400-5. (PMID: 10618430)