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

作者：Jodi L. McGill, Randy E. Sacco, Cynthia L. Baldwin, Janice C. Telfer, Mitchell V. Palmer, Wade Ray Waters · 发表于：The Journal of Immunology · 年份：2014 · DOI：10.4049/jimmunol.1302567 · 被引用次数：61 · 研究领域：Mycobacterium research and diagnosis、Tuberculosis Research and Epidemiology、Immune Cell Function and Interaction

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 un...