AN HLA-A2-RESTRICTED TYROSINASE ANTIGEN ON MELANOMA-CELLS RESULTS FROM POSTTRANSLATIONAL MODIFICATION AND SUGGESTS A NOVEL PATHWAY FOR PROCESSING OF MEMBRANE-PROTEINS

T lymphocytes recognize antigens consisting of peptides presented by c lass I and II major histocompatibility complex (MHC) molecules. The pe ptides identified so far have been predictable from the amino acid seq uences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cel ls. The peptide results from posttranslational conversion of asparagin e to aspartic acid. This change is of central importance for peptide r ecognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has n ot been previously described for any MHC-associated peptide and repres ents the first demonstration of posttranslational modification of a na turally processed class I-associated peptide. This observation is rele vant to the identification and prediction of potential peptide antigen s. The most likely mechanism for production of this peptide leads to t he suggestion that antigenic peptides can be derived from proteins tha t are translated into the endoplasmic reticulum.