title: Specific recognition of mycobacterial protein and peptide antigens by γδ T cell subsets following infection with virulent Mycobacterium bovis.
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.
authors.affiliation: Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA 50010;
authors.forename: Jodi L
authors.initials: JL
authors.lastname: McGill
authors.forename: Randy E
authors.initials: RE
authors.lastname: Sacco
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Baldwin
authors.forename: Janice C
authors.initials: JC
authors.lastname: Telfer
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Palmer
authors.forename: W Ray
authors.initials: WR
authors.lastname: Waters
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000382:microbiology; D014774:Virulence / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C086500:DMBT1 protein, Bos taurus; C505464:ESAT-6-CFP10 fusion protein; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma