PMID: 8598464Jan 1, 1996Paper

Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1-restricted immune repertoire to melanoma

The Journal of Immunology : Official Journal of the American Association of Immunologists
A AnichiniG Parmiani

Abstract

To determine whether HLA-A21 restricted melanoma Ags exist that are not expressed on normal melanocytes, a panel of 478 T cell clones from six HLA-A21+ patients was selected for HLA-A2 restricted lysis of autologous tumor and then tested for differential recognition of HLA-A2.1+ melanomas and normal melanocytes. Four subsets of clones were identified in the panel of 107 HLA-A2-restricted CTL clones. CTL clones from three of the four subsets did not lyse melanocytes, but recognized fresh HLA-A2.1+ melanomas and defined three classes of epitopes, including unique Ags, common melanoma Ags, and Ags shared with neoplastic cells of different histologic origin. These CTL clones did not recognize any of the 10 peptides selected for specific association to HLA-A2.1 and derived from Melan-A/Mart-1, tyrosinase, gp100, or MAGE-3 proteins. By contrast, the fourth subset of HLA-A2.1-restricted CTl clones recognized both melanoma and melanocytes. These CTL clones were directed to a peptide from either Melan-A/Mart-1, tyronise, or gp100. By a limiting dilution assay, designed to evaluate the frequency of HLA-A2-restricted CTL precursors (CTLp) directed to melanoma but not to melanocytes, such precursors were found in the peripheral blood or tu...Continue Reading

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