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

Author

Listed:
  • Erin W. Meermeier

    (Oregon Health and Science University)

  • Bruno F. Laugel

    (Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine)

  • Andrew K. Sewell

    (Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine)

  • Alexandra J. Corbett

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne)

  • Jamie Rossjohn

    (Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine
    School of Biomedical Sciences, Monash University
    ARC Centre of Excellence in Advanced Molecular Imaging, Monash University)

  • James McCluskey

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne)

  • Melanie J. Harriff

    (Oregon Health and Science University
    VA Portland Health Care Center)

  • Tamera Franks

    (VA Portland Health Care Center)

  • Marielle C. Gold

    (Oregon Health and Science University
    Oregon Health and Science University
    VA Portland Health Care Center)

  • David M. Lewinsohn

    (Oregon Health and Science University
    Oregon Health and Science University
    VA Portland Health Care Center)

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.

Suggested Citation

  • Erin W. Meermeier & Bruno F. Laugel & Andrew K. Sewell & Alexandra J. Corbett & Jamie Rossjohn & James McCluskey & Melanie J. Harriff & Tamera Franks & Marielle C. Gold & David M. Lewinsohn, 2016. "Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12506
    DOI: 10.1038/ncomms12506
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