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Recognition of vitamin B metabolites by mucosal-associated invariant T cells

Author

Listed:
  • Onisha Patel

    (School of Biomedical Sciences, Monash University)

  • Lars Kjer-Nielsen

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

  • Jérôme Le Nours

    (School of Biomedical Sciences, Monash University
    Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University)

  • Sidonia B. G. Eckle

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

  • Richard Birkinshaw

    (School of Biomedical Sciences, Monash University)

  • Travis Beddoe

    (School of Biomedical Sciences, Monash University
    Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University)

  • Alexandra J. Corbett

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

  • Ligong Liu

    (Institute for Molecular Bioscience, The University of Queensland)

  • John J. Miles

    (Queensland Institute of Medical Research and Australian Centre for Vaccine Development
    Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park)

  • Bronwyn Meehan

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

  • Rangsima Reantragoon

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

  • Maria L. Sandoval-Romero

    (School of Biomedical Sciences, Monash University)

  • Lucy C. Sullivan

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

  • Andrew G. Brooks

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

  • Zhenjun Chen

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

  • David P. Fairlie

    (Institute for Molecular Bioscience, The University of Queensland)

  • James McCluskey

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

  • Jamie Rossjohn

    (School of Biomedical Sciences, Monash University
    Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University
    Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park)

Abstract

The mucosal-associated invariant T-cell antigen receptor (MAIT TCR) recognizes MR1 presenting vitamin B metabolites. Here we describe the structures of a human MAIT TCR in complex with human MR1 presenting a non-stimulatory ligand derived from folic acid and an agonist ligand derived from a riboflavin metabolite. For both vitamin B antigens, the MAIT TCR docks in a conserved manner above MR1, thus acting as an innate-like pattern recognition receptor. The invariant MAIT TCR α-chain usage is attributable to MR1-mediated interactions that prise open the MR1 cleft to allow contact with the vitamin B metabolite. Although the non-stimulatory antigen does not contact the MAIT TCR, the stimulatory antigen does. This results in a higher affinity of the MAIT TCR for a stimulatory antigen in comparison with a non-stimulatory antigen. We formally demonstrate a structural basis for MAIT TCR recognition of vitamin B metabolites, while illuminating how TCRs recognize microbial metabolic signatures.

Suggested Citation

  • Onisha Patel & Lars Kjer-Nielsen & Jérôme Le Nours & Sidonia B. G. Eckle & Richard Birkinshaw & Travis Beddoe & Alexandra J. Corbett & Ligong Liu & John J. Miles & Bronwyn Meehan & Rangsima Reantragoo, 2013. "Recognition of vitamin B metabolites by mucosal-associated invariant T cells," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3142
    DOI: 10.1038/ncomms3142
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    Cited by:

    1. Mark Walkenhorst & Jana K. Sonner & Nina Meurs & Jan Broder Engler & Simone Bauer & Ingo Winschel & Marcel S. Woo & Lukas Raich & Iris Winkler & Vanessa Vieira & Lisa Unger & Gabriela Salinas & Olivie, 2024. "Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Kensuke Shibata & Chihiro Motozono & Masamichi Nagae & Takashi Shimizu & Eri Ishikawa & Daisuke Motooka & Daisuke Okuzaki & Yoshihiro Izumi & Masatomo Takahashi & Nao Fujimori & James B. Wing & Takahi, 2022. "Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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