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

Peptides derived from the melanoma‐associated MART‐1/Melan‐A antigen are currently implemented in immunotherapy for inducing or augmenting T‐cell responses directed against peptides expressed by autologous tumor cells in HLA‐A2+ patients with melanoma. Here, we describe the specificity of the T‐cell clone SK29‐FFM1.1, which secretes GM‐CSF in response to a panel of synthetic MART‐1/Melan‐A‐derived peptides, including the naturally presented ILTVILGVL32–40, but exhibits cytotoxicity and IFN‐γ secretion exclusively to the MART‐1/Melan‐A derived peptide AAGIGILTV27–35. In addition, cytotoxic T‐lymphocyte (CTL) clone SK29‐FFM1.1 recognizes 3 different naturally processed and presented peptides on HLA‐A2+ MART‐1/Melan‐A+ melanoma cells, as defined by cytotoxicity and IFN‐γ and GM‐CSF secretion. Processing and presentation of MART‐1/Melan‐A peptides appears to be different in cells of non‐melanocytic origin, as shown by the characterization of naturally presented peptides displayed by HLA‐A2+ colorectal cancer cells transduced with a MART‐1/Melan‐A gene–containing retrovirus. Our data suggest that multiple epitopes, including ILTVILGVL and different isoforms of AAGIGILTV derived from MART‐1/Melan‐A may be naturally presented by melanoma cells to the immune system. Int. J. Cancer81:979–984, 1999. © 1999 Wiley‐Liss, Inc.

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