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

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 ly mphocytes 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 pr oduction of cytokines, These effecters were directed against the tyrosinase -related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw 8, The nonamer and decamer peptides containing the sequence ANDPIFVVL (resi dues 387-395) of TRP-2 and the octamer, nonamer, acid decamer peptides cont aining the sequence SNDGPTLI (residues 71-78) of gp100 reconstituted the ep itope 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 f orms 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 mela noma patient studied. Together these data indicate that HLA-Cw8 can restric t the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptide s could stimulate a patient's PBL, suggesting that these Ags could have con tributed to a systemic immunity against melanoma.