Abstract
In the last five years, knowledge of human tumor antigens recognized by autologous cytolytic T lymphocytes (CTL) has increased considerably. So far, genetic and biochemical approaches have led to the molecular identification of three classes of antigens. Most of these antigens consist of peptides that are presented to T cells by HLA molecules. The first class comprises antigens encoded by genes such as MAGE, BAGE, and GAGE, which are expressed in various tumors of different histological origins, but not in normal tissues other than testis. The second class represents differentiation antigens encoded by genes that are only expressed in melanoma and normal melanocytes like tyrosinase, Melan-A/MART-1, gp100 and gp75. The third class includes antigens produced by unique point mutations in genes that are ubiquitously expressed. In most cases, the antigenic peptide is encoded by the mutated region of the gene. A number of these antigens provide promising targets for new protocols of specific cancer immunotherapy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 1957; 18:769.
Rouse BT, Röllinghoff M, Warner NL. Anti-θ serum-induced suppression of the cellular transfer of tumour-specific immunity to a syngeneic plasma cell tumour. Nature New Biol 1972; 238:116.
Brunner KT, McDonald HR, Cerottini J-C. Quantification and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors. J Exp Med 1981; 154:362.
Anichini A, Fossati G, Parmiani G. Clonal analysis of the cytolytic T-cell response to human tumors. Immunol Today 1987; 8:385.
Bruggen P van der, Traversari C, Chomez P, Lurquin C, DePlaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254:1643.
Traversi C, Bruggen P van der, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E. Amar-Costesec A, Boon T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med 1992; 176:1453.
Wöffel T, Van Pel A, Brichard V, Schneider J, Seliger B, Meyer zum Büschenfelde K-H, Boon T. Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 1994; 24:759.
Cox AL, Skipper J, Chen Y, Henderson RA, Darrow TL, Shabanowitz J, Engelhard VH, Hunt DF, Slingluff CL Jr. Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 1994; 264:716.
Jung S, Schluesener HJ. Human T lymphocytes recognize a peptide of single point-mutated, oncogenic ras proteins. J Exp Med 1991; 173:273.
Celis E, Tsai V, Crimi C, DeMars R, Wentworth PA, Chesnut RW, Grey HM, Sette A, Serra HM. Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes. Proc Natl Acad Sci USA 1994; 91:2105.
Bruggen P van der, Bastin J, Gajewski T, Coulie PG, BoËl P, De Smet C, Traversari C, Townsend A, Boon T. A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Immunol 1994; 24:3038.
De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora J-P, De Smet C, Brasseur F, Bruggen P van der, Lethé B, Lurquin C, Brasseur R, Chomez P, De Backer O, Cavenee W, Boon T. Structure, chromosomal localization and expression of twelve genes of the MAGE family. Immunogenetics 1994; 40:360.
BoËl P, Wildmann C, Sensi M-L, Brasseur R, Renauld J-C, Coulie P, Boon T, Bruggen P van der. BAGE, a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 1995; 2:167.
Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995; 182:689.
Brasseur F, Marchand M, Vanwijck R, Hérin M, Lethé B, Chomez P, Boon T. Human gene MAGE-1, which codes for a tumor rejection antigen, is expressed by some breast tumors. Int J Cancer 1992; 52:839.
Brasseur F, Rimoldi D, Liénard D, Lethé B, Carrel S, Arienti F, Suter L, Vanwijck R, Bourlond A, Humblet Y, Vacca A, Conese M, Lahaye T, Degiovanni G, Deraemaecker R, Beauduin M, Sastre X, Salamon E, Dréno B, JÄger E, Knuth A, Chevreau C, Suciu S, Lachapelle M, Pouillart P, Parmiani G, Lejeune F, Cerottini J-C, Boon T, Marchand M. Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer 1995: 63:375.
Weynants P, Lethé B, Brasseur F, Marchand M, Boon T. Expression of MAGE genes by non-small-cell lung carcinomas. Int J Cancer 1994; 56:826.
Bruggen P van der, Szikora J-P, BoËl P, Wildmann C, Somville M, Sensi M, Boon T. Autologous cytolytic T lymphocytes recognize a MAGE-1 nonapeptide on melanomas expressing HLA-Cw*1601. Eur J Immunol 1994; 24:2134.
Gaugler B, Van den Eynde B, Bruggen P van der, Romero P, Gaforio JJ, De Plaen E, Lethé B, Brasseur F, Boon T. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 1994: 179:921.
Herman J, Bruggen P van der, Luescher I, Mandruzzato S, Romero P, Thonnard J, Fleischhauer K, Boon T, Coulie PG. A peptide encoded by human gene MAGE-3 and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Immunogenetics 1996; 43:377.
Takahashi K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis. Cancer Res 1995: 55:3478.
Chomez P, Williams R, De Backer O, Boon T, Vennström B. The SMAGE gene family is expressed in post-meiotic spermatids during mouse germ cell differentiation. Immunogenetics 1995; 43:97.
Haas GG Jr, D’Cruz OJ, De Bault LE. Distribution of human leukocyte antigen-ABC and -D/DR antigens in the unfixed human testis. Am J Reprod Immunol Microbiol 1988; 18:47.
Uyttenhove C, Godfraind C, Lethé B, Amar-Costesec A, Renauld J-C, Gajewski TF, Duffour T, Warnier G, Boon T, Van den Eynde BJ. The expression of mouse gene P1A in testis does not prevent safe induction of cytolytic T cells against a P1A-encoded tumor antigen. Int J Cancer. In Press
De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 1996; 93:7149.
Guilloux Y, Lucas S, Brichard VG, Van Pel A, Viret C, De Plaen E, Brasseur F, Lethé B, Jotereau F, Boon T. A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas in encoded by an intron sequence of the N-acetylglucosaminyltransferase V gene. J Exp Med 1996; 183:1173.
Gaugler B, Brouwenstijn N, Vantomme V, Szikora J-P, Van der Spek CW, Patard J-J, Boon T, Schrier P, Van den Eynde BJ. A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma. Immunogenetics 1996;44:323.
Ressing ME, Sette A, Brandt RMP, Ruppert J, Wentworth PA, Hartman M, Oseroff C, Grey HM, Melief CJM, Kast WM. Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. J Immunol 1995; 154:5934.
Anichini A, Maccalli C, Mortarini R, Salvi S, Mazzocchi A, Squarcina P, Herlyn M, Parmiani G. Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients. J Exp Med 1993:177:989.
Brichard V, Van Pel A, Wölfel T, Wölfel C, De Plaen E, Lethé B, Coulie P, Boon T. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1993; 178:489.
Coulie PG, Brichard V, Van Pel A, Wölfel T, Schneider J, Traversari C, Mattel S, De Plaen E, Lurquin C, Szikora J-P, Renauld J-C, Boon T. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994; 180:35.
Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 1994; 91:3515.
Bakker ABH, Schreurs MWJ, Boer AJ de, Kawakami Y, Rosenberg SA, Adema GJ, Figdor CG. Melanocyte lineage-specific antigen gp l00 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med 1994; 179:1005.
Wang R-F, Robbins PF, Kawakami Y, Kang X-Q, Rosenberg SA. Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes. J Exp Med 1995; 181:799.
Robbins PF, El-Gamil M, Kawakami Y, Rosenberg SA. Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy. Cancer Res 1994; 54:3124.
Brichard VG, Herman J, Van Pel A, Wildmann C, Gaugier B, Wölfel T, Boon T, Lethé 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.
Topalian SL, Rivoltini L, Mancini M, Markus NR, Robbins PF, Kawakami Y, Rosenberg SA. Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci USA 1994; 91:9461.
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 1994; 91:6458.
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 1994; 180:347.
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 gp l00 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol 1995; 154:3961.
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.
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.
Skipper JCA, Hendrickson RC, Gulden PH, Brichard V, Van Pel A, Chen Y, Shabanowitz J, Wölfel T, Slingluff CL Jr, 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 1996; 183:527.
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.
Wang R-F, 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 1996; 183:1131.
Mattes MJ, Thomson TM, Old LJ, Lloyd KO. A pigmentationassociated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum. Int J Cancer 1983; 32:717.
Bystryn J-C, Darrell R, Friedman RJ, Kopf A. Prognostic significance of hypopigmentation in malignant melanoma. Arch Dermatol 1987; 123:1053.
Richards JM, Mehta N, Ramming K, Skosey P. Sequential chemoimmunotherapy in the treatment of metastatic melanoma. J Clin Oncol 1992; 10:1338.
Boon T. Toward a genetic analysis of tumor rejection antigens. Adv Cancer Res 1992:58:177.
Mandelboim O, Berke G, Fridkin M, Feldman M, Eisenstein M, Eisenbach L. CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma. Nature 1994; 369:67.
Monach PA, Meredith SC, Siegel CT, Schreiber H. A unique tumor antigen produced by a single amino acid substitution. Immunity 1995; 2:45.
Coulie PG, Lehmann F, Lethé B, Herman J, Lurquin C, Andrawiss M, Boon T. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci USA 1995; 92:7976.
Wölfel T, Hauer M, Schneider J, Serrano M, Wölfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Büschenfelde K-H, Beach D. A pl6INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 1995; 269:1281.
Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA. A mutated Β-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 1996; 183:1185.
BrÄndie D, Brasseur F, Weynants P, Boon T, Van den Eynde B. A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma. J Exp Med 1996; 183:2501.
Marchand M, Weynants P, Rankin E, Arienti F, Belli F, Parmiani G, Cascinelli N, Bourlond A, Vanwijck R, Humblet Y, Canon J-L, Laurent C, Naeyaert J-M, Plagne R, Deraemaeker R, Knuth A, JÄger E, Brasseur F, Herman J, Coulie PG, Boon T. Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer 1995; 63:883.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Van den Eynde, B.J., Boon, T. Tumor antigens recognized by T lymphocytes. Int J Clin Lab Res 27, 81–86 (1997). https://doi.org/10.1007/BF02912440
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02912440