Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles

Yutaka Kawakami, Paul F. Robbins, Xiang Wang, Janis P. Tupesis, Maria R. Parkhurst, Xiaoqiang Kang, Kazuyasu Sakaguchi, Ettore Appella, Steven A. Rosenberg

研究成果: Article

97 引用 (Scopus)

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To isolate melanoma Ags recognized by T cells, cDNA libraries made from melanoma cell lines were screened with four CTLs derived from tumor infiltrating lymphocytes (TIL) that were able to recognize melanoma cells in a HLA-A1, -A2, or -A3 restricted manner. Although cDNAs encoding the previously identified melanoma Ags, tyrosinase and gp100, were isolated, these TIL were found to recognize previously unidentified peptides. An HLA- A1-restricted CTL, TIL1388, was found to recognize a tyrosinase peptide (SSDYVIPIGTY), and an HLA-A3-restricted CTL, TIL1351, recognized a gp100 peptide (LIYRRRLMK). CTL clones isolated from the HLA-A2-restricted TIL1383 recognized a gp100 peptide (RLMKQDFSV). HLA-A2-restricted CTL, TIL1200, recognized a gp100 peptide (RLPRIFCSC). Replacement of either cysteine residue with α-amino butyric acid in the gp100 peptide, RLPRIFCSC, enhanced CTL recognition, suggesting that the peptide epitope naturally presented on the tumor cell surface may contain reduced cysteine residues. Oxidation of these cysteines might have occurred during the course of the synthesis or pulsing of the peptide in culture. These modifications may have important implications for the development of efficient peptide-based vaccines. These newly identified peptide epitopes can extend the ability to perform immunotherapy using synthetic peptides to a broader population of patients, especially those expressing HLA-A1 or HLA-A3 for whom only a few melanoma epitopes have previously been identified.

元の言語English
ページ(範囲)6985-6992
ページ数8
ジャーナルJournal of Immunology
161
発行部数12
出版物ステータスPublished - 1998 12 15

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ASJC Scopus subject areas

  • Immunology

これを引用

Kawakami, Y., Robbins, P. F., Wang, X., Tupesis, J. P., Parkhurst, M. R., Kang, X., Sakaguchi, K., Appella, E., & Rosenberg, S. A. (1998). Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles. Journal of Immunology, 161(12), 6985-6992.