2. Academic Validation
  3. Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

  • Nat Commun. 2016 Aug 16;7:12506. doi: 10.1038/ncomms12506.
Erin W Meermeier 1,  Bruno F Laugel 2,  Andrew K Sewell 2,  Alexandra J Corbett 3,  Jamie Rossjohn 2 4 5,  James McCluskey 3,  Melanie J Harriff 6 7,  Tamera Franks 7,  Marielle C Gold 1 6 7,  David M Lewinsohn 1 6 7
Affiliations

Affiliations

  • 1 Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239 USA.
  • 2 Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
  • 3 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
  • 4 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
  • 5 ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
  • 6 Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
  • 7 Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.
PMID: 27527800 DOI: 10.1038/ncomms12506
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.

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