Cytotoxic T lymphocytes define multiple peptide isoforms derived from the melanoma-associated antigen MART-1/Melan-A

Peptides derived from the melanoma-associated MART-II Melan-A antigen are c urrently implemented in immunotherapy for inducing or augmenting T-cell res ponses directed against peptides expressed by autologous tumor cells in HLA -A2(+) patients with melanoma. Here, we describe the specificity of the T-c ell clone SK29-FFM 1.1, which secretes CM-CSF in response to a panel of syn thetic MART-I/Melan-A-derived peptides, including the naturally presented I LTVIL-GVL(32-40), but exhibits cytotoxicity and IFN-gamma secretion exclusi vely to the MART-I/Melan-A-derived peptide AAGIGILTV(27-35). In addition, c ytotoxic T-lymphocyte (CTL) clone SK29-FFM I,I recognizes 3 different natur ally processed and presented peptides on HLA-A2(+) MART-I/Melan-A(+) melano ma cells, as defined by cytotoxicity and IFN-gamma and GM-CSF secretion. Pr ocessing and presentation of MART-I/Melan-A peptides appears to be differen t in cells of non-melanocytic origin, as shown by the characterization of n aturally presented peptides displayed by HLA-A2(+) colorectal cancer cells transduced with a MART-I/Melan-A gene-containing retrovirus. Our data sugge st that multiple epitopes, including ILTVIL-GVL and different isoforms of A AGIGILTV derived from MART-I/Melan-A may be naturally presented by melanoma cells to the immune system. (C) 1999 Wiley-Liss, Inc.