SHAVED EPITOPES FOR HLA-A3-RESTRICTED MELANOMA-REACTIVE HUMAN CTL INCLUDE A NATURALLY PROCESSED EPITOPE FROM PMEL-17 GP100/

Human CD8(+) CTL recognize peptides bound to class I MHC molecules on the surface of melanoma cells. Several peptides derived from melanocyt e lineage-specific proteins have been identified as epitopes for HLA-A 2 restricted melanoma-reactive CTL. Because less than half of melanoma patients express HLA-A2, it is important to identify CTL epitopes res tricted by other common MHC molecules including HLA-A1 and -A3, We hav e generated HLA-A3-restricted human CTL that recognize one or more sha red melanoma Ags. All of the melanomas recognized by one of these CTL lines express Pmel-17/gp100, and those that fail to express this Ag ar e not lysed, This CTL line also specifically recognizes the lymphoblas toid line C1R-A3 following infection with a recombinant vaccinia encod ing the melanocyte lineage-specific protein Pmel-17/gp100, Thus, at le ast one Pmel-17/gp100 peptide is an epitope for this CTL line, We have identified ALLAVGATK (Pmel-17/gp100 residues 17-25) as an epitope for this CTL line and have shown that it is naturally processed and prese nted by HLA-A3 on melanoma cells, A second HLA-A3-restricted melanoma- reactive CTL line recognizes at least one additional shared epitope. T hese findings suggest that cellular immune responses directed against multiple shared melanoma epitopes exist in the 20 to 25% of melanoma p atients who express HLA-A3, In addition, immunotherapy directed agains t Pmel-17/gp100 and other shared melanoma Ags may be useful in a large subset of these patients.