Evidence for a stepwise evolution of the CD3 family

The three CD3 components of the TCR complex are encoded as clustered genes in mammals. The evolution of such a multimeric complex is likely to occur s tepwise. The chicken CD3 cluster was entirely sequenced, and, in contrast t o mammals, only two chicken CD3 genes were found to be physically linked to the unrelated genes HZW10 and epithelial V-like Ag flanking both sides of the CD3 cluster. Biochemical analyses of CD3 immunoprecipitates confirmed t he presence of only two CD3 proteins and revealed an essential role for CD3 gamma delta glycosylation during assembly.. Functional analyses indicated that the chicken TCR/CD3 complex was efficiently down-regulated by phorbol ester treatment, demonstrating the integrity of a CD3 gamma-like cytoplasmi c internalization motif. These data argue for a stepwise CD3 evolution, wit h major differences in the TCR/CD3 structure between mammalian and nommamma lian vertebrates setting a basis for the understanding of the CD3 phylogeny and proving the ancestral nature of the CD3 gamma delta protein.