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 s hared by a number of histologically different rumors. Till date, only human and mouse MAGE genes have been characterized. Our study describes the firs t non-mammalian member of MAGE super-family, DMAGE from D. melanogaster. A conceptual translation of the cDNA of DMAGE identifies a putative protein t hat contains a motif that shares eight out of nine amino acids with the pre viously 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 ye ars earlier in evolution than the emergence of the adaptive immune system o f higher vertebrates. Northern analysis revealed that DMAGE is a developmen tally regulated gene highly expressed in adult fruit Ay and in the embryo o f D. melanogaster. In contrast, the expression level of the mRNA of DMAGE i n fruit fly larva is substantially lower than in embryo and adult fly. We p ropose that studies of DMAGE on D. melanogaster may help define the functio n(s) of MAGE super-family genes. (C) 2000 Elsevier Science Ltd. All rights reserved.