γδ TCRs Function as Innate-like Receptors in the Bovine γδ T Cell Response against Leptospira

Leptospira serovar Hardjo are bacterial pathogens of cattle that also cause zoonotic disease in humans. Vaccine-mediated protection against Leptospira serovar Hardjo in cattle is associated with a workshop cluster 1 (WC1)(+) gamma delta T cell response that can be recalled in vitro from PBMC by antigenic stimulation. This provides a model system in which to examine protective vaccine-induced gamma delta T cell responses in a gamma delta T cell high species. Only a small proportion (5-10%) of WC1(+) gamma delta T cells from immunized cattle are Leptospira responders, implying that Ag specificity is determined by clonally distributed receptors. Both WC1 and TCR are known to be required for Leptospira-specific responses by bovine WC1(+) gamma delta T cells. Through variegated expression patterns and V(D)J recombination, respectively, they have the capacity to confer Ag specificity. In this study, we develop and use a high-throughput TCR-sequencing approach to study the TCR gamma and TCR delta repertoires of naive ex vivo PBMC, Leptospira-responding, and Leptospira nonresponding WC1(+) gamma delta T cells to examine the potential role of gamma delta TCR in determining Ag specificity. Our results provide novel insights into the PBMC gamma delta TCR repertoires in cattle, demonstrating the TCR gamma repertoire to be clonally stratified and essentially public, whereas the TCR delta repertoire shows much higher levels of clonal diversity and is essentially private. TCR repertoire analysis of Leptospira-responding WC1(+) gamma delta T cells identifies no signature of TCR-mediated selection, suggesting that TCR functions largely as an innate-like receptor and does not act as a primary determinant of Ag specificity in the response to this pathogen.

Automated summary

This study investigates the TCR repertoires in cattle and finds that the TCR gamma repertoire is clonally stratified and essentially public, while the TCR delta repertoire shows higher levels of clonal diversity and is essentially private. Furthermore, the study suggests that TCR functions mainly as an innate-like receptor and does not act as a primary determinant of antigen specificity in the response to Leptospira.