IDENTIFICATION OF EPITOPE MIMICS RECOGNIZED BY CTL REACTIVE TO THE MELANOMA MELANOCYTE-DERIVED PEPTIDE MART-1(27-35)/

CTL reactivity to the epitope MART-1((27-35)), of tile melanoma (self) antigen MART-1/melan A is frequently observed in Tumor-infiltrating l ymphocytes and may be readily elicited from tile peripheral blood of m elanoma patients that express HLA-A0201. Available data suggest that these observations contrast with those made for other HLA-A0201-prese nted melanoma self antigens regarding the regularity observed CTL resp onses. Based on preliminary findings, we hypothesized that the CTL res ponse to MART-1 might be augmented in part by T cell encounters with p eptides derived from sources other than MART-1, which show sequence si milarity to MART-1((27-35)). To test this idea, a protein database sea rch fur potential MART-1 epitope mimics was done using criteria develo ped from analyses of effector recognition of singley-substituted pepti de analogues of MART-1((27-35)). Synthetic peptides were made for a po rtion of the sequences retrieved; 12/40 peptides tested were able to s ensitize target cells for lysis by one or more anti-MART-1 effectors. The peptides recognized correspond to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV-1; cells infec ted with recombinant vaccinia virus encoding native glycoprotein C wer e lysed by anti-MART-1 effectors. Our results overall indicate that se quences conforming to the A2.1 binding motif and possessing features e ssential to recognition by anti-MART-1 CTL occur frequently in protein s. These findings further suggest that T cells might encounter a varie ty of such sequences in vivo, and chat epitope mimicry may Flay a role in modulating the CTL response to MART-1((27-35)).