title: Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss.
abstract: B7-H3 is a novel protein structurally related to the B7 family of ligands by the presence of a single set of immunoglobulin-V-like and immunoglobulin-C-like (VC) domains. By multiplex PCR, the dominantly expressed form of human B7-H3 was found to be a splice variant containing tandemly duplicated VC domains (VCVC). In contrast, mouse B7-H3 cDNA contained only one single VC form due to an exon structure corresponding to V-(pseudoexon C)-(pseudoexon V)-C. Comparisons of human, monkey, mouse, and hamster genomic B7-H3 reveal that primates, but not rodents, exhibited a higher degree of intramolecular sequence similarity between VC duplications than between molecules. Both VC and VCVC forms of human B7-H3 inhibited CD4(+) T cell proliferation and downregulated cytokine production upon TCR activation. These results suggest independent, but convergent, paths of B7-H3 active domain duplication followed by divergent histories of exon degeneration in rodents and exon maintenance by humans.
authors.affiliation: Wyeth Research, 200 Cambridge Park Drive, 02140, Cambridge, MA, USA. VLing@compoundtherapeutics.com
authors.forename: Vincent
authors.initials: V
authors.lastname: Ling
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wu
authors.forename: Vikki
authors.initials: V
authors.lastname: Spaulding
authors.forename: Jan
authors.initials: J
authors.lastname: Kieleczawa
authors.forename: Deborah
authors.initials: D
authors.lastname: Luxenberg
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Carreno
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics* / Q000502:physiology; D006224:Cricetinae; D019143:Evolution, Molecular; D005091:Exons; D020440:Gene Duplication; D000882:Haplorhini / Q000235:genetics; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics* / Q000502:physiology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011971:Receptors, Immunologic
chemical_list: D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; C486038:Cd276 protein, mouse; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D011971:Receptors, Immunologic