Cloning of the first invertebrate MAGE paralogue: an epitope that activates T-cells in humans is highly conserved in evolution.
The MAGE (Melanoma Associated Antigen) family tumor-specific antigens are shared by a number of histologically different tumors. Till date, only human and mouse MAGE genes have been characterized. Our study describes the first non-mammalian member of MAGE super-family, DMAGE from D. melanogaster. A conceptual translation of the cDNA of DMAGE identifies a putative protein that contains a motif that shares eight out of nine amino acids with the previously identified promiscuous, HLA-A2 restricted antigenic epitope in the C-terminus of human MAGE-B1 and -B2. Similarly, this motif of DMAGE shares seven out of nine amino acids with the same antigenic epitope of human MAGE-A3 and -A12. Thus, the phylogeny of proteins that activate tumor specific T-cells in mammals as unmutated self-proteins began at least 100 million years earlier in evolution than the emergence of the adaptive immune system of higher vertebrates. Northern analysis revealed that DMAGE is a developmentally regulated gene highly expressed in adult fruit fly and in the embryo of D. melanogaster. In contrast, the expression level of the mRNA of DMAGE in fruit fly larva is substantially lower than in embryo and adult fly. We propose that studies of DMAGE on D. melanogaster may help define the function(s) of MAGE super-family genes.
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Brentwood Biomedical Research Institute, Veterans Affairs West Los Angeles Medical Center, CA 90073, USA. maalpold@msn.com
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D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000145:classification / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D017931:DNA Primers; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian; D015723:Gene Library; D015789:HLA-A2 Antigen; D019476:Insect Proteins / Q000235:genetics*; D007814:Larva; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D013045:Species Specificity
D000951:Antigens, Neoplasm; D017931:DNA Primers; D015789:HLA-A2 Antigen; D019476:Insect Proteins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger