title: Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens.
abstract: Mucosal-associated invariant T (MAIT) cells are thought to detect microbial antigens presented by the HLA-Ib molecule MR1 through the exclusive use of a TRAV1-2-containing TCRα. Here we use MR1 tetramer staining and ex vivo analysis with mycobacteria-infected MR1-deficient cells to demonstrate the presence of functional human MR1-restricted T cells that lack TRAV1-2. We characterize an MR1-restricted clone that expresses the TRAV12-2 TCRα, which lacks residues previously shown to be critical for MR1-antigen recognition. In contrast to TRAV1-2(+) MAIT cells, this TRAV12-2-expressing clone displays a distinct pattern of microbial recognition by detecting infection with the riboflavin auxotroph Streptococcus pyogenes. As known MAIT antigens are derived from riboflavin metabolites, this suggests that TRAV12-2(+) clone recognizes unique antigens. Thus, MR1-restricted T cells can discriminate between microbes in a TCR-dependent manner. We postulate that additional MR1-restricted T-cell subsets may play a unique role in defence against infection by broadening the recognition of microbial metabolites.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239 USA.
authors.forename: Erin W
authors.initials: EW
authors.lastname: Meermeier
authors.affiliation: Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Bruno F
authors.initials: BF
authors.lastname: Laugel
authors.affiliation: Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Corbett
authors.affiliation: Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.|Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.|Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Harriff
authors.affiliation: Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.
authors.forename: Tamera
authors.initials: T
authors.lastname: Franks
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239 USA.|Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.|Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.
authors.forename: Marielle C
authors.identifier: 0000-0003-2505-3291
authors.initials: MC
authors.lastname: Gold
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239 USA.|Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.|Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
mesh_terms: D000072283:A549 Cells; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D012256:Riboflavin / Q000276:immunology* / Q000378:metabolism; D013290:Streptococcal Infections / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012256:Riboflavin