Genomic evolution of the B7 family (63.28)

Abstract

Abstract B7 ligands are expressed by different cell types and interact with receptors on T cells to generate signals required for immunoregulation. All B7 members have structurally distinct domains in the immunoglobulin superfamily (IgSF). Some variable (V) domains of B7 ligands contain an ancestral, so-called “VJ” IgSF domain, while some constant (C) domains are of the “C1-type,” a rare form found primarily in molecules associated with adaptive immunity. Phylogenetic analysis had suggested a relationship between the V domains of B7 and MHC-linked tapasin (TAPBP), suggesting that they share a common ancestor. To study the evolutionary origins and functional aspects of B7 ligands, we used a comparative genomics approach emphasizing the genome of the amphibian Xenopus, a high-connectivity model. All known B7 family members except CD80 were found in X. tropicalis. Some B7 genes show conserved synteny between human and frog, suggesting that they are ancient and thus vital for the immune system, while the other genes were taxon-specific, perhaps having novel functions. In a more thorough bioinformatics approach, we found un-assigned B7 family genes from different vertebrate taxa including human. One of these genes is B7-H6 and the Xenopus orthologue is linked to beta-2 microglobulin (B2M). B2M is MHC-linked in sharks, presumably in the primordial organization. Thus, linkage of a B7 precursor to the MHC seems to be ancestral as part of the pre-adaptive immune complex.