Evolution and Selection of Primate T Cell Antigen Receptor BV8 Gene Subfamily

Abstract

The set of potential T cell receptor specificities is highly diverse. The relative contributions of T cell receptor (TCR) Vβ gene segment polymorphisms, duplications, deletions, and gene conversions to this final T cell receptor protein diversity are unknown. To study these mechanisms, we sequenced and compared closely related primate TCR gene segments from BV8S1, S2, and S5. Interspecies comparisons show that these gene segments have sustained multiple duplication, gene conversion, and deletion events during the last 35 million years of anthropoid primate evolution. BV8 coding sequences are generally conserved with respect to their flanking noncoding sequences, but we find no evidence for positive or negative selection in sequences coding for the first two putative complementarity-determining (ligand-binding) regions. Sequences of TCRBV8 gene segments from unrelated humans demonstrate no nonsynonymous substitutions in nonleader regions of either the BV8S1 or S2 gene segments. We conclude that gene duplication, deletion, and conversion mechanisms contribute in a substantial way to the overall diversity of the TCRBV8 gene segment repertoire in primate evolution and that germline substitutions and consequent polymorphisms in CDRs 1 and 2 of these gene segments probably do not play an active role in generating TCR β chain protein variation.