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Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

Jodi L. McGill, Randy E. Sacco, Cynthia L. Baldwin, Janice C. Telfer, Mitchell V. Palmer, W. Ray Waters
Journal of immunology 2014 v.192 no.6 pp. 2756-2769
proteins, humans, interleukin-17, direct contact, cattle, models, mice, bacterial antigens, tuberculosis, immune response, CD4-positive T-lymphocytes, Mycobacterium bovis, virulence, culture filtrates
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 'd T cells from virulent M. bovis infected cattle respond specifically and directly to complex, protein and non-protein mycobacterial antigens. Importantly, we demonstrate for the first time that bovine 'd T cells specifically recognize small peptide antigens derived from the mycobacterial protein complex early secreted antigenic target 6 kDa protein:10 kDa culture filtrate protein (ESAT6:CFP10) and that this recognition requires direct contact with APC, but is independent of MHC class 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 'd T cells, are the primary source of this critical pro-inflammatory mediator. Bovine 'd T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1). We demonstrate that the M. bovis-specific 'd T cell response is composed of a heterogeneous mix of WC1-expressing populations, with WC1.1+ and WC1.2+ subsets responding in vitro to mycobacterial antigens, and both subsets accumulating in the lesions of M. bovis infected animals. The results described herein enhance our understanding of 'd T cell biology and, as virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of 'd T cells in the mycobacterial-specific immune response.