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Human melanoma cell line MZ2-MEL expresses several antigens recognized by autologous cytolytic T lymphocyte (CTL) clones. We reported previously the identification of a gene, named MAGE-1, that codes for one of these antigens named MZ2-E. We show here that antigen MZ2-D, which is present on the same tumor, is encoded by another member of the MAGE gene family named MAGE-3. Like MAGE-1, MAGE-3 is composed of three exons and the large open reading frame is entirely located in the third exon. Its sequence shows 73% identity with MAGE-1. Like MZ2-E, antigen MZ2-D is presented by HLA-A1. The antigenic peptide of MZ2-D is a nonapeptide that is encoded by the sequence of MAGE-3 that is homologous to the MAGE-1 sequence coding for the MZ2-E peptide. Competition experiments using single Ala-substituted peptides indicated that amino acid residues Asp in position 3 and Tyr in position 9 were essential for binding of the MAGE-1 peptide to HLA-A1. Gene MAGE-3 is expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes. It is expressed in a larger proportion of melanoma samples than MAGE-1. MAGE-3 encoded antigens may therefore have a wide applicability for specific immunotherapy of melanoma patients.

Type

Journal article

Journal

J Exp Med

Publication Date

01/03/1994

Volume

179

Pages

921 - 930

Keywords

Adult, Amino Acid Sequence, Antigens, Neoplasm, Base Sequence, Binding Sites, Breast Neoplasms, Carcinoma, Squamous Cell, Cell Line, Exons, Female, Fetus, Genomic Library, HLA-A1 Antigen, Head and Neck Neoplasms, Humans, Lung Neoplasms, Male, Melanoma, Melanoma-Specific Antigens, Molecular Sequence Data, Neoplasm Proteins, Oligodeoxyribonucleotides, Open Reading Frames, Organ Specificity, T-Lymphocytes, Cytotoxic, Testis, Tumor Cells, Cultured