{gamma}{delta} TCRs Function as Innate-like Receptors in the Bovine {gamma}{delta} T Cell Response against Leptospira [ANTIGEN RECOGNITION AND RESPONSES]

Key Points

This is the first description, to our knowledge, of bovine γδ TCR repertoires using the NGS approach.

In the bovine γδ T cell response against Leptospira, TCRs function as innate-like receptors.

Abstract

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)+ γδ 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 γδ T cell responses in a γδ T cell high species. Only a small proportion (5–10%) of WC1+ γδ 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+ γδ 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 TCRγ and TCRδ repertoires of naive ex vivo PBMC, Leptospira-responding, and Leptospira nonresponding WC1+ γδ T cells to examine the potential role of γδ TCR in determining Ag specificity. Our results provide novel insights into the PBMC γδ TCR repertoires in cattle, demonstrating the TCRγ repertoire to be clonally stratified and essentially public, whereas the TCRδ repertoire shows much higher levels of clonal diversity and is essentially private. TCR repertoire analysis of Leptospira-responding WC1+ γδ 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.

Footnotes

This work was supported by a U.S. Department of Agriculture National Institute of Food and Agriculture Agriculture and Food Research Initiative Animal Health Award made to C.L.B. (2016-09379), an EU Horizon 2020 Framework Programme Grant (VetBioNet; Grant 731014), and a Biotechnology and Biological Sciences Research Council Institute Strategic Programmes Grant (BBS/E/D/20002174).

The online version of this article contains supplemental material.

Abbreviations used in this article:

D50Diversity 50HTShigh-throughput sequencingTRDTCRδTRGTCRγWC1workshop cluster 1Received April 29, 2022.Accepted September 6, 2022.Copyright © 2022 by The American Association of Immunologists, Inc.

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