A PEPTIDE ENCODED BY HUMAN GENE MAGE-3 AND PRESENTED BY HLA-A2 INDUCES CYTOLYTIC T-LYMPHOCYTES THAT RECOGNIZE TUMOR-CELLS EXPRESSING MAGE-3

The human MAGE-3 gene is expressed in many tumors of several histologi cal types but it is silent in normal tissues, with the exception of te stis. Antigens encoded by MAGE-3 may, therefore, be useful targets for specific anti-tumor immunization of cancer patients. We reported prev iously that MAGE-3 codes for an antigenic peptide recognized on a mela noma cell line by autologous cytolytic T lymphocytes (CTL) restricted by HLA-A1. Here we report that the MAGE-3 gene also codes for another antigenic peptide that is recognized by CTL restricted by HLA-A2. MAGE -3 peptides bearing consensus anchor residues for HLA-A2 were synthesi zed and tested for binding. T lymphocytes from normal individuals were stimulated with autologous irradiated lymphoblasts pulsed with each o f three peptides that showed strong binding to HLA-A2. Peptide FLWGPRA LV was able to induce CTL. We obtained CTL clones that recognized not only HLA-A2 cells pulsed with this peptide but also HLA-A2 tumor cell lines expressing the MAGE-3 gene. The proportion of melanoma tumors ex pressing this antigen should be approximately 32 % in Caucasian popula tions, since 49 % of individuals carry the HLA-A2 allele and 65% of me lanomas express MAGE-3.