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 stepwise. The chicken CD3 cluster was entirely sequenced, and, in contrast to 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 the presence of only two CD3 proteins and revealed an essential role for CD3gammadelta 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 CD3gamma-like cytoplasmic internalization motif. These data argue for a stepwise CD3 evolution, with major differences in the TCR/CD3 structure between mammalian and nonmammalian vertebrates setting a basis for the understanding of the CD3 phylogeny and proving the ancestral nature of the CD3gammadelta protein.