Structure, diversity and expression of the TCRδ chains in the Mexican axolotl

Abstract

Mammals and birds have two major populations of T cells, based on the molecular composition and biological properties of their antigen receptors (TCR). αβ T cells recognize antigenic peptides linked to major histocompatibility complex (MHC) molecules, and γδ T cells recognize native peptide or non-peptide antigens independently of MHC. Very little is known about γδ T cells in ectothermic vertebrates. We have cloned and characterized the TCRδ chains of an urodele amphibian, the Mexican axolotl (Ambystoma mexicanum). The Cδ domain is structurally similar to its mammalian homologues and the transmembrane domain is very well conserved. Four of the six Vα regions that can associate with Cα (Vα2, Vα3, Vα5 and Vα6) can also associate with Cδ, but no specific Vδ regions were found. This suggests that the axolotl TRD locus is nested within the TRA locus, as in mammals, and that this organization has been present in all tetrapod vertebrates and in the common ancestor of Lissamphibians and mammals, for over 400 million years. Two Jδ regions were identified, but no Dδ segments were clearly recognized at the Vδ-Jδ junctions. This results in shorter and less variable CDR3 loops than in other vertebrates and the size range of the Vδ-Jδ junctions is similar to that of mammalian immunoglobulin light chains. Equivalent quantities of TRD mRNA were found in the lymphoid organs, and in the skin and the intestines of normal and thymectomized axolotls. The analysis of several Vα/δ6-Cδ and Vβ7-Cβ junctions showed that both the TCRδ and the TCRβ chains were limited in diversity in thymectomized axolotls.