Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss

Genomics. 2003 Sep;82(3):365-77. doi: 10.1016/s0888-7543(03)00126-5.


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.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • B7 Antigens
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / physiology
  • Cricetinae
  • Evolution, Molecular*
  • Exons
  • Gene Duplication*
  • Haplorhini / genetics
  • Humans
  • Immunoglobulin Constant Regions / genetics*
  • Immunoglobulin Constant Regions / physiology
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin Variable Region / physiology
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • Receptors, Immunologic


  • Antigens, CD
  • B7 Antigens
  • B7-1 Antigen
  • CD276 protein, human
  • Cd276 protein, mouse
  • Immunoglobulin Constant Regions
  • Immunoglobulin Variable Region
  • Receptors, Immunologic