Spectratype analysis of the T cell receptor δ CDR3 region of bovine γδ T cells responding to leptospira

Abstract

Gamma delta T cells comprise the majority of blood T cells in ruminants at birth and remain at high levels for several years with most expressing the WC1 co-receptor. A subpopulation of Bos taurus WC1(+) cells expressing a restricted set of WC1 molecules respond immediately by proliferation and interferon-γ production to leptospira following vaccination, preceding the response by CD4 T cells. Our goal is to define the γδ T cell recognition elements involved. Previously, we showed that the responding cells employed a variety of TRDV genes indicating that the CDR1 and CDR2 of TCRδ could vary and may not be principally involved in antigen specificity. Murine and human γδ T cells bind T22 and self lipids through their CDR3δ. Like mice, cattle use up to five TRDD genes in a single CDR3δ adding flexibility to length and configuration for antigen binding. Here, we used spectratyping to evaluate the CDR3δ of leptospira-responsive cells. Little or no compartmentalization of CDR3δ was found for antigen-responsive cells that incorporated TRDV1, TRDV2, or TRDV3 even though they comprise the majority of the leptospira-responding population. Compartmentalization occurred for TRDV4-containing transcripts and was maintained over time and among cattle. However, no common amino acid motif was apparent in those CDR3δ sequences, although a bias in D gene usage occurred. We hypothesize that the restricted set of WC1 co-receptors expressed by the responding cells may lend specificity to the response through their ability to bind bacteria facilitating interaction of various TCRs with bacterial components resulting in cross-linking and activation.