A NEW FAMILY OF GENES-CODING FOR AN ANTIGEN RECOGNIZED BY AUTOLOGOUS CYTOLYTIC T-LYMPHOCYTES ON A HUMAN-MELANOMA

Human melanoma MZ2-MEL expresses several distinct antigens that are re cognized by autologous cytolytic T lymphocytes (CTL). Some of these an tigens are encoded by genes MAGE-1, MAGE-3, and BAGE, which are expres sed in a large fraction of tumors of various histological types but ar e silent in normal adult tissues with the exception of testis. We repo rt here the identification of the gene coding for MZ2-F, another antig en recognized by autologous CTL on MZ2-MEL cells. This gene, which was named GAGE-1, is not related to any presently known gene. It belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. Antigenic peptide YRPRPRRY, which is encoded by GAGE-1, is recognized by anti-MZ2-F CTL on class I molecule HLA-Cw6. The two genes of the CAGE family that code for thi s peptide, namely GAGE-1 and GAGE-2, are expressed in a significant pr oportion of melanomas (24%), sarcomas (25%), non-small cell lung cance rs (19%), head and neck tumors (19%), and bladder tumors (12%). About 50% of melanoma patients carry on their tumor at least one of the pres ently defined antigens encoded by the MAGE, BAGE, and GAGE genes.