Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with Virulent Mycobacterium bovis.

TitleSpecific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with Virulent Mycobacterium bovis.
Publication TypeJournal Article
Year of Publication2014
AuthorsMcGill, JL, Sacco, RE, Baldwin, CL, Telfer, JC, Palmer, MV, Waters, RW
JournalJ Immunol
Date Published2014 Feb 14
Abstract

Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that γδ T cells from virulent M. bovis-infected cattle respond specifically and directly to complex, protein, and nonprotein mycobacterial Ags. Importantly, to our knowledge, we demonstrate for the first time that bovine γδ T cells specifically recognize peptide Ags derived from the mycobacterial protein complex ESAT6:CFP10 and that this recognition requires direct contact with APCs and signaling through the T cell Ag receptor but is independent of MHC class I or II. Furthermore, we show that M. bovis infection in cattle induces robust IL-17A protein responses. Interestingly, in contrast to results from mice, bovine CD4 T cells, and not γδ T cells, are the predominant source of this critical proinflammatory mediator. Bovine γδ T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1), and we demonstrate that the M. bovis-specific γδ T cell response is composed of a heterogeneous mix of WC1-expressing populations, with the serologically defined WC1.1(+) and WC1.2(+) subsets responding in vitro to mycobacterial Ags and accumulating in the lesions of M. bovis-infected animals. The results described in this article enhance our understanding of γδ T cell biology and, because virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of γδ T cells in the mycobacterial-specific immune response.

Alternate JournalJ. Immunol.