Novel HLA-Cw8-restricted T cell epitopes derived from tyrosinase- related protein-2 and gp100 melanoma antigens

Chiara Castelli, Paolo Tarsini, Arabella Mazzocchi, Francesca Rini, Licia Rivoltini, Fernando Ravagnani, Francesco Gallino, Filiberto Belli, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

The identification of T cell epitopes presented by alternative HLA-B and -C alleles may provide a means to counteract the tumor escape mechanism based on the selection of tumor cells no longer susceptible to HLA-A-restricted T cell recognition. Several T cell clones and lines were obtained from T lymphocytes purified from melanoma-infiltrated or noninfiltrated lymph nodes of a patient who remained disease free 8 yr after surgery. Selected T cells recognized the autologous melanoma as evaluated by direct cytolysis and production of cytokines. These effectors were directed against the tyrosinase-related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw8. The nonamer and decamer peptides containing the sequence ANDPIFVVL (residues 387-395) of TRP-2 and the octamer, nonamer, and decamer peptides containing the sequence SNDGPTLI (residues 71-78) of gp100 reconstituted the epitope for TRP-2- and gp100-specific T cell lines and clones, respectively. However, only the nonameric form of TRP-2 and the nonameric and octameric forms of gp100 were able to induce peptide-specific T cells recognizing the autologous tumor in an HLA-class I-restricted fashion from PBMC of the melanoma patient studied. Together these data indicate that HLA-Cw8 can restrict the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptides could stimulate a patient's PBL, suggesting that these Ags could have contributed to a systemic immunity against melanoma.

Original languageEnglish
Pages (from-to)1739-1748
Number of pages10
JournalJournal of Immunology
Volume162
Issue number3
Publication statusPublished - Feb 1 1999

ASJC Scopus subject areas

  • Immunology

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