A MAGE-6-encoded peptide is recognized by expanded lymphocytes infiltrating a spontaneously regressing human primary melanoma lesion

In recent years, experiments based on the in vitro stimulation of either au tologous peripheral blood lymphocytes or tumor-infiltrating lymphocytes wit h melanoma cells have shown that distinct members of the large MAGE gene fa mily encode tumor-associated antigenic peptides. However, little is still k nown about natural anti-MAGE responses in vivo. We have studied a case of s pontaneously regressing human melanoma, hypothesizing that in this unique s ituation, the host immune system had developed an efficient cytotoxic T lym phocyte (CTL) response against the cancer cells. Amongst the dense tumor in filtrate certain clonal populations of T cells were shown to be amplified, thereby suggesting that an antigen-driven selection had occurred at the tum or site. One of the expanded tumor-infiltrating lymphocytes was shown to be a V beta 13(+) CD8(+) CTL displaying a strong and selective cytotoxic acti vity against the autologous melanoma cells. Here we show that this cytotoxi c T cell clone recognizes a MAGE-6-encoded peptide. MAGE-6 is therefore the fourth gene of the MAGE family shown to encode antigenic peptide recognize d by T cells. Together, these data provide further evidence that T cell res ponses against MAGE antigens may naturally develop in vivo.