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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Jul 1;180(1):347–352. doi: 10.1084/jem.180.1.347

Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes

PMCID: PMC2191573  PMID: 7516411

Abstract

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase- related protein-1 (gp75) were evaluated for recognition by HLA-A2- restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.

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Selected References

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  1. 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 Apr 1;177(4):989–998. doi: 10.1084/jem.177.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bakker A. B., Schreurs M. W., de Boer A. J., Kawakami Y., Rosenberg S. A., Adema G. J., Figdor C. G. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med. 1994 Mar 1;179(3):1005–1009. doi: 10.1084/jem.179.3.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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 Aug 1;178(2):489–495. doi: 10.1084/jem.178.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen T., Muller R. M., Tomita Y., Shibahara S. Nucleotide sequence of the cDNA encoding human tyrosinase-related protein. Nucleic Acids Res. 1990 May 11;18(9):2807–2808. doi: 10.1093/nar/18.9.2807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  6. Gaugler B., Van den Eynde B., van der Bruggen P., Romero P., Gaforio J. J., 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 Mar 1;179(3):921–930. doi: 10.1084/jem.179.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hom S. S., Schwartzentruber D. J., Rosenberg S. A., Topalian S. L. Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. J Immunother Emphasis Tumor Immunol. 1993 Jan;13(1):18–30. doi: 10.1097/00002371-199301000-00003. [DOI] [PubMed] [Google Scholar]
  8. Hom S. S., Topalian S. L., Simonis T., Mancini M., Rosenberg S. A. Common expression of melanoma tumor-associated antigens recognized by human tumor infiltrating lymphocytes: analysis by human lymphocyte antigen restriction. J Immunother (1991) 1991 Jun;10(3):153–164. [PubMed] [Google Scholar]
  9. Hunt D. F., Henderson R. A., Shabanowitz J., Sakaguchi K., Michel H., Sevilir N., Cox A. L., Appella E., Engelhard V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science. 1992 Mar 6;255(5049):1261–1263. doi: 10.1126/science.1546328. [DOI] [PubMed] [Google Scholar]
  10. Kawakami Y., Eliyahu S., Delgado C. H., Robbins P. F., Rivoltini L., Topalian S. L., Miki T., Rosenberg S. A. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515–3519. doi: 10.1073/pnas.91.9.3515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kawakami Y., Rosenberg S. A., Lotze M. T. Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma. J Exp Med. 1988 Dec 1;168(6):2183–2191. doi: 10.1084/jem.168.6.2183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kawakami Y., Zakut R., Topalian S. L., Stötter H., Rosenberg S. A. Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. J Immunol. 1992 Jan 15;148(2):638–643. [PubMed] [Google Scholar]
  13. Knuth A., Wölfel T., Klehmann E., Boon T., Meyer zum Büschenfelde K. H. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2804–2808. doi: 10.1073/pnas.86.8.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. O'Neil B. H., Kawakami Y., Restifo N. P., Bennink J. R., Yewdell J. W., Rosenberg S. A. Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. J Immunol. 1993 Aug 1;151(3):1410–1418. [PMC free article] [PubMed] [Google Scholar]
  15. Rosenberg S. A., Packard B. S., Aebersold P. M., Solomon D., Topalian S. L., Toy S. T., Simon P., Lotze M. T., Yang J. C., Seipp C. A. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988 Dec 22;319(25):1676–1680. doi: 10.1056/NEJM198812223192527. [DOI] [PubMed] [Google Scholar]
  16. Rosenberg S. A., Spiess P., Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986 Sep 19;233(4770):1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
  17. Ruppert J., Sidney J., Celis E., Kubo R. T., Grey H. M., Sette A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929–937. doi: 10.1016/0092-8674(93)90472-3. [DOI] [PubMed] [Google Scholar]
  18. Shilyansky J., Nishimura M. I., Yannelli J. R., Kawakami Y., Jacknin L. S., Charmley P., Rosenberg S. A. T-cell receptor usage by melanoma-specific clonal and highly oligoclonal tumor-infiltrating lymphocyte lines. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2829–2833. doi: 10.1073/pnas.91.7.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Slingluff C. L., Jr, Cox A. L., Henderson R. A., Hunt D. F., Engelhard V. H. Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes. J Immunol. 1993 Apr 1;150(7):2955–2963. [PubMed] [Google Scholar]
  20. Storkus W. J., Zeh H. J., 3rd, Maeurer M. J., Salter R. D., Lotze M. T. Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. J Immunol. 1993 Oct 1;151(7):3719–3727. [PubMed] [Google Scholar]
  21. Traversari C., van der Bruggen P., Luescher I. F., 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 Nov 1;176(5):1453–1457. doi: 10.1084/jem.176.5.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wölfel T., Klehmann E., Müller C., Schütt K. H., Meyer zum Büschenfelde K. H., Knuth A. Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med. 1989 Sep 1;170(3):797–810. doi: 10.1084/jem.170.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen 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 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]

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