CYTOLYTIC T-CELL REACTIVITY AGAINST MELANOMA-ASSOCIATED DIFFERENTIATION ANTIGENS IN PERIPHERAL-BLOOD OF MELANOMA PATIENTS AND HEALTHY-INDIVIDUALS

Antigenic peptides derived from several differentiation antigens of th e melanocyte lineage were recently identified in human melanomas as ta rgets for HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs). To exami ne their potential role in tumour-directed immune responses in vivo, w e determined CTL reactivity against seven antigenic peptides derived f rom the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens in the pe ripheral blood of 10 HLA-A2+ healthy controls and 26 HLA-A2+ melanoma patients. The influenza matrix peptide (GILGFVFTL) presented by HLA-A2 .1 was used as a control peptide. CTL reactivity was assessed in a mix ed lymphocyte 'peptide' culture assay. Reactivity against Melan A/MART -1-derived peptide antigens was readily detectable in both melanoma pa tients and controls. Reactivity directed against tyrosinase-derived pe ptide antigens was also detected in both melanoma patients and healthy individuals, but less frequently. A measurable response against gp100 /Pmel17-derived antigens was found in 1/10 controls and in 1/26 of the melanoma patients. Reactivity against the influenza matrix peptide wa s common in both melanoma patients and controls. Our findings show tha t precursor CTLs against melanocyte differentiation antigens can be de tected in peripheral blood of melanoma patients and healthy individual s. The pattern of CTL reactivity directed against melanoma-associated antigens does not seem to be altered in melanoma patients. Despite ant igen-specific CTL reactivity, tumour growth was not prevented in melan oma patients and autoimmune phenomena were not detected in healthy ind ividuals. It remains to be determined whether precursor CTLs recognizi ng melanocyte differentiation antigens can be activated by immunizatio n and lead to effective tumour rejection in vivo.