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Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis
- McGill, Jodi L., Sacco, Randy E., Baldwin, Cynthia L., Telfer, Janice C., Palmer, Mitchell V., Waters, W. Ray
- 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.