A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma.
Human melanoma MZ2-MEL expresses several distinct antigens that are recognized by autologous cytolytic T lymphocytes (CTL). Some of these antigens are encoded by genes MAGE-1, MAGE-3, and BAGE, which are expressed in a large fraction of tumors of various histological types but are silent in normal adult tissues with the exception of testis. We report here the identification of the gene coding for MZ2-F, another antigen recognized by autologous CTL on MZ2-MEL cells. This gene, which was named GAGE-1, is not related to any presently known gene. It belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. Antigenic peptide YRPRPRRY, which is encoded by GAGE-1, is recognized by anti-MZ2-F CTL on class I molecule HLA-Cw6. The two genes of the GAGE family that code for this peptide, namely GAGE-1 and GAGE-2, are expressed in a significant proportion of melanomas (24%), sarcomas (25%), non-small cell lung cancers (19%), head and neck tumors (19%), and bladder tumors (12%). About 50% of melanoma patients carry on their tumor at least one of the presently defined antigens encoded by the MAGE, BAGE, and GAGE genes.
Van den Eynde
B
B
Ludwig Institute for Cancer Research, Brussels Branch, Belgium.
Peeters
O
O
De Backer
O
O
Gaugler
B
B
Lucas
S
S
Boon
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005333:Fetus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015236:HLA-C Antigens / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000276:immunology; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016415:Sequence Alignment; D017385:Sequence Homology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; C092706:BAGE protein, human; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D000939:Epitopes; C095365:GAGE1 protein, human; C095366:GAGE2A protein, human; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm