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Characterization of Antigens Recognized by T Cells on Human Tumors

  • Conference paper
Symposium in Immunology VI

  • 41 Accesses

Abstract

Tumor immunology has come into the limelight since the realization that antitumor cytotoxic T lymphocytes (CTLs), which constitute the major effectors involved in tumor rejection, can be cultured in vitro and used as tools to identify the target antigens expressed by the tumor cells (Boon et al. 1994). Tumor-specific CTLs have been found in most mouse tumor models, and in several human tumor types, mainly in melanoma. By using a genetic approach based on the transfection of genomic or cDNA libraries, we cloned the genes encoding a number of melanoma antigens. This led to the molecular identification of these antigens which usually consist of a peptide derived from an intracellular protein and presented to CTLs by an HLA class I molecule. On the basis of their pattern of expression, these antigens can be classified into three groups. Antigens of the first group are encoded by genes that are expressed in the tumor cells but are silent in normal adult tissues except the testis. The second group consists of differentiation antigens that are expressed in melanoma and in normal melanocytes. Antigens of the third group are unique to individual tumors and appear through tumor-specific mutations in genes expressed ubiquitously.

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References

  • Bakker ABH, Schreurs MWJ, de Boer AJ, Kawakami Y, Rosenberg SA, Adema GJ, Figdor CG, (1994) Melanocyte lineage-specific antigen gpioo is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med 179: 1005–1009

    CAS  Google Scholar 

  • Boël P, Wildmann C, Sensi M-L, Brasseur R, Renauld J-C, Coulie P, Boon T, van der Bruggen P (1995) BAGE, a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2: 167–175

    Article  PubMed  Google Scholar 

  • Boon T (1992) Toward a Genetic Analysis of Tumor Rejection Antigens. Adv Cancer Res 58: 177–210

    Article  PubMed  CAS  Google Scholar 

  • Boon T, Cerottini J-C, Van den Eynde B, van der Bruggen P, Van Pel A (1994) Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 12:337–365

    Google Scholar 

  • Brandie D, Brasseur F, Weynants P, Boon T, Van den Eynde B (1996) A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma. J Exp Med 183: 2501–2508

    Article  Google Scholar 

  • Brasseur F, Marchand M, Vanwijck R, Hérin M, Lethé B, Chomez P, Boon T (1992) Human gene MAGE-1, which codes for a tumor rejection antigen, is expressed by some breast tumors. Int J Cancer 52: 839–841

    Article  PubMed  CAS  Google Scholar 

  • 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, (1995) Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer 63: 375–380

    Article  PubMed  CAS  Google Scholar 

  • Brichard V, Van Pel A, Wölfel T, Wölfel C, De Plaen E, Lethé B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178: 489–495

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Bystryn J-C, Darrell R, Friedman RJ, Kopf A (1987) Prognostic significance of hypo-pigmentation in malignant melanoma. Arch Dermatol 123: 1053–1055

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Coulie PG, Brichard V, Van Pel A, Wölfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora J-P, Renauld J-C, Boon T (1994) A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 180: 35–42

    Article  PubMed  CAS  Google Scholar 

  • Coulie PG, Lehmann F, Lethé B, Herman J, Lurquin C, Andrawiss M, Boon T (1995) A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci USA 92: 7976–7980

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora J-P, De Smet C, Brasseur F, van der Bruggen P, Lethé B, Lurquin C, Brasseur R, Chomez P, De Backer O, Cavenee W, Boon T, (1994) Structure, chromosomal localization and expression of twelve genes of the MAGE family. Immunogenetics 40: 360–369

    Article  PubMed  CAS  Google Scholar 

  • Gaugler B, Van den Eynde B, van der Bruggen P, Romero P, Gaforio JJ, De Plaen E, Lethé B, Brasseur F, Boon T, (1994) Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T Iymphocytes. J Exp Med 179: 921–930

    Article  PubMed  CAS  Google Scholar 

  • Gaugler B, Brouwenstijn N, Vantomme V, Szikora J-P, Van der Spek CW, Patard JJ, Boon T, Schrier P, Van den Eynde BJ, (1996) A new gene coding for an antigen recognized by autologous CTL on a human renal carcinoma. Immunogenetics 44 323–330

    Google Scholar 

  • Guilloux Y, Lucas S, Brichard VG, Van Pel A, Viret C, De Plaen E, Brasseur F, Lethé B, Jotereau F, Boon T (1996) A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the Nacetylglucosaminyltransferase V gene. J Exp Med 183: 1173–1183

    Article  PubMed  CAS  Google Scholar 

  • Haas GG Jr, D’Cruz OJ, De Bault LE (1988)Distribution of human leukocyte antigen-ABC and -D/DR antigens in the unfixed human testis. Am J Reprod Immunol Microbiol 18: 47–51

    Google Scholar 

  • Herman J, van der Bruggen P, Luescher I, Mandruzzato S, Romero P, Thonnard J, Fleischhauer K, Boon T, Coulie PG (1996) 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 43: 377–383

    Article  PubMed  CAS  Google Scholar 

  • Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA (1994a) Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 91: 3515–3519

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA (1994c) Identification of the immunodominant peptides of the MART- 1 human melanoma antigen recognized by the majority of HLA-A2restricted tumor infiltrating lymphocytes. J Exp Med 180: 347–352

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Mandelboim O, Berke G, Fridkin M, Feldman M, Eisenstein M, Eisenbach L (1994) CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma. Nature 369: 67–71

    Article  PubMed  CAS  Google Scholar 

  • 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, Brasseu F, Herman J, Coulie PG, Boon T, (1995) Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer 63: 883–885

    Article  PubMed  CAS  Google Scholar 

  • Monach PA, Meredith SC, Siegel CT, Schreiber H (1995) A unique tumor antigen produced by a single amino acid substitution. Immunity 2:45–59

    Article  PubMed  CAS  Google Scholar 

  • Richards JM, Mehta N, Ramming K, Skosey P (1992) Sequential chemoimmunotherapy in the treatment of metastatic melanoma. J Clin Oncol 10:1338–1343

    Google Scholar 

  • Robbins PF, El-Gamil, M, Kawakami Y, Rosenberg SA (1994) Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy. Cancer Res 54: 3124–3126

    PubMed  CAS  Google Scholar 

  • Sensi ML, Traversari C, Radrizzani M, Salvi S, Maccalli C, Mortarini R, Rivoltini L, Farina C, Nicolini G, Wölfel T, Brichard V, Boon T, Bordignon C, Anichini A, Parmiani G, (1995) Cytotoxic T-lymphocyte clones from different patients display limited T-cell-receptor variable-region gene usage in HLA-A2-restricted recognition of the melanoma antigen Melan-A/MART-1. Proc Natl Acad Sci USA 92: 5674–5678

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Shichijo S, Noguchi M, Hirohata M, Itoh K (1995) Identification of MAGE-i and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis. Cancer Res 55:3478–3482

    Google Scholar 

  • Topalian SL, Rivoltini L, Mancini M, Markus NR, Robbins PF, Kawakami Y, Rosenberg SA (1994) Human CD4 + T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci USA 91: 9461–9465

    Article  PubMed  CAS  Google Scholar 

  • Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L, Boon T (1992a) Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T Iymphocytes. Immunogenetics 35:145–152

    Article  CAS  Google Scholar 

  • Traversari C, van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E, Amar-Costesec A, Boon T (1992b) A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-Ai by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med 176: 1453–1457

    Article  PubMed  CAS  Google Scholar 

  • Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T (1995) A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 182: 689–698

    Article  PubMed  Google Scholar 

  • van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643–1647

    Article  PubMed  Google Scholar 

  • van der Bruggen P, Szikora J-P, Boël P, Wildmann C, Somville M, Sensi M, Boon T (1994a) Autologous cytolytic T lymphocytes recognize a MAGE-1 nonapeptide on melanomas expressing HLA-Cw*1601. Eur J Immunol 24: 2134–2140

    Article  PubMed  Google Scholar 

  • van der Bruggen P, Bastin J, Gajewski T, Coulie PG, Boël P, De Smet C, Traversari C, Townsend A, Boon T (1994b) 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 24: 3038–3043

    Article  PubMed  Google Scholar 

  • Wang R-F, Robbins PF, Kawakami Y, Kang X-Q, Rosenberg SA (1995). Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes. J Exp Med 181: 799–804

    Article  PubMed  CAS  Google Scholar 

  • Weynants P, Lethé B, Brasseur F, Marchand M, Boon T (1994) Expression of MAGE genes by non-small cell lung carcinomas. Int J Cancer 56: 826–829

    Article  PubMed  CAS  Google Scholar 

  • Wölfel T, Van Pel A, Brichard V, Schneider J, Seliger B, Meyer zum Büschenfelde K-H, Boon T (1994) Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 24: 759–764

    Article  PubMed  Google Scholar 

  • 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 (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T Iymphocytes in a human melanoma. Science 269: 1281–1284

    Article  PubMed  Google Scholar 

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Authors
  1. B. J. Van Den Eynde
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  2. B. Gaugler
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  3. D. Brändle
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  4. Y. Guilloux
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  5. P. Van Der Bruggen
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  6. P. Coulie
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  7. V. Brichard
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  8. T. Boon
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Editor information

Editors and Affiliations

  1. Institut für Immunologie der Universität Wien, Borschkegasse 8 a, 1090, Wien, Austria

    Martha M. Eibl

  2. Department of Hematology, Johannes Gutenberg Universität, Langenbeckstr. 1, 55101, Mainz, Germany

    Christoph Huber

  3. Abteilung für Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik, Hugstetter Str. 55, 79106, Freiburg, Germany

    Hans H. Peter

  4. Pädiatrische Pneumologie und Immunologie, Universitäts-Klinikum Rudolf-Virchow, Standort Charlottenburg Heubnerweg 6, 14059, Berlin, Germany

    Ulrich Wahn

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© 1997 Springer-Verlag Berlin Heidelberg

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Van Den Eynde, B.J. et al. (1997). Characterization of Antigens Recognized by T Cells on Human Tumors. In: Eibl, M.M., Huber, C., Peter, H.H., Wahn, U. (eds) Symposium in Immunology VI. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60562-8_1

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  • DOI: https://doi.org/10.1007/978-3-642-60562-8_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-61755-6

  • Online ISBN: 978-3-642-60562-8

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