Chicken T-cell receptor β-chain diversity: An evolutionarily conserved Dβ-encoded glycine turn within the hypervariabfe CDR3 domain

Abstract

Unlike mammals, chickens generate an immunoglobulin (Ig) repertoire by a developmentally regulated process of intrachromosomal gene conversion, which results in nucleotide substitutions throughout the variable regions of the Ig heavy- and light-chain genes. In contrast to chicken Ig genes, we show in this report that diversity of the rearranged chicken T-cell receptor (TCR) β-chain gene is generated by junctional heterogeneity, as observed in rearranged mammalian TCR genes. This junctional diversity increases during chicken development as a result of an increasing base-pair addition at the Vβ-Dβ and Dβ-Jβ joints (where V, D, and J are the variable, diversity, and joining gene segments). Despite the junctional hypervariability, however, almost all functional Vβ-Dβ-Jβ junctions appear to encode a glycine-containing β-turn. Such a turn may serve to position the amino acid side chains of a hypervariable TCR β-chain loop with respect to the antigen-binding groove of the major histocompatibility complex molecule. Consistent with this hypothesis, the germ-line Dβ nucleotide sequences of chickens, mice, rabbits, and humans have been highly conserved and encode a glycine in all three reading frames.