A PEPTIDE ENCODED BY THE HUMAN MAGE3 GENE AND PRESENTED BY HLA-B44 INDUCES CYTOLYTIC T-LYMPHOCYTES THAT RECOGNIZE TUMOR-CELLS EXPRESSING MAGE3

The human MAGE3 gene is expressed in a significant proportion of tumor s of various histological types, but is silent in normal adult tissues other than testis and placenta. Antigens encoded by MAGE3 may therefo re be useful targets for specific antitumor immunization. Two antigeni c peptides encoded by the MAGE3 gene have been reported previously. On e is presented to cytolytic T lymphocytes (CTL) by HLA-A1, the other b y HLA-A2 molecules, Here we show that MAGE3 also codes for a peptide t hat is presented to CTL by HLA-B44. MAGE3 peptides containing the HLA- B44 peptide binding motif were synthesized, Peptide MEVDPIGHLY, which showed the strongest binding to HLA-844, was used to stimulate blood T lymphocytes from normal HLA-B44 donors. CTL clones were obtained that recognized not only HLA-B44 cells sensitized with the peptide, but al so HLA-B44 tumor cell lines expressing MAGE3. The proportion of metast atic melanomas expressing the MAGE3/HLA-B44 antigen should amount to a pproximately 17% in the Caucasian population, since 24% of individuals carry the HLA-B44 allele and 76% of these tumors express MAGE3.