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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

Yi Zhang^*, Pascal Chaux^2,*, Vincent Stroobant^*, Alexander M. M. Eggermont, Jurgen Corthals, Bernard Maillère, Kris Thielemans, Marie Marchand^*, Thierry Boon^* and Pierre van der Bruggen^3,*

^* Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, Brussels, Belgium; Rotterdam Cancer Institute and University Hospital, Rotterdam, The Netherlands; Laboratory of Physiology, Medical School, Vrije Universiteit Brussel, Brussels, Belgium; and Département d’Ingénierie et d’Etudes des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif-sur-Yvette, France

"Cancer-germline" 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. MAGE-3 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 MAGE-3 peptide, which is recognized by three different CD4⁺ T cell clones isolated from a melanoma patient vaccinated with a MAGE-3 protein. These clones, which express different TCRs, recognize on HLA-DR1 peptide ACYEFLWGPRALVETS, which corresponds to the MAGE-3_267–282 and the MAGE-12_267–282 protein sequences. One of the T cell clones, which expresses LFA-1 at a high level, lysed tumor cells expressing DR1 and MAGE-3. 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.

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