A MAGE-3 Peptide Presented by HLA-DR1 to CD4+ T Cells That Were Isolated from a Melanoma Patient Vaccinated with a MAGE-3 Protein1

"Cancergermline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in normal tissues. They encode shared tumor specific Ags, which have been used in therapeutic vaccination trials of cancer patients. MAGE3 is expressed in 74% of metastatic melanoma and in 50% of carcinomas of esophagus, head and neck, bladder, and lung. We report here the identification of a new MAGE3 peptide, which is recognized by three different CD4+ T cell clones isolated from a melanoma patient vaccinated with a MAGE3 protein. These clones, which express different TCRs, recognize on HLADR1 peptide ACYEFLWGPRALVETS, which corresponds to the MAGE 3267 282 and the MAGE12267 282 protein sequences. One of the T cell clones, which expresses LFA-1 at a high level, lysed tumor cells expressing DR1 and MAGE3. Another of these DR1-restricted CD4+ clones recognized not only the MAGE-3/12 peptide but also homologous peptides encoded by genes MAGE-1, 2, 4, 6, 10, and 11.