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MR1 presents microbial vitamin B metabolites to MAIT cells

Author

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  • Lars Kjer-Nielsen

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Onisha Patel

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia)

  • Alexandra J. Corbett

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Jérôme Le Nours

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia)

  • Bronwyn Meehan

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Ligong Liu

    (Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia)

  • Mugdha Bhati

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia)

  • Zhenjun Chen

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Lyudmila Kostenko

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Rangsima Reantragoon

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • Nicholas A. Williamson

    (Metabolomics Australia, University of Melbourne, Parkville, Victoria 3010, Australia)

  • Anthony W. Purcell

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Metabolomics Australia, University of Melbourne, Parkville, Victoria 3010, Australia)

  • Nadine L. Dudek

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Metabolomics Australia, University of Melbourne, Parkville, Victoria 3010, Australia)

  • Malcolm J. McConville

    (Metabolomics Australia, University of Melbourne, Parkville, Victoria 3010, Australia)

  • Richard A. J. O’Hair

    (School of Chemistry, Bio21 Molecular Science and Biotechnology Institute and ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia)

  • George N. Khairallah

    (School of Chemistry, Bio21 Molecular Science and Biotechnology Institute and ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia)

  • Dale I. Godfrey

    (University of Melbourne, Parkville, Victoria 3010, Australia)

  • David P. Fairlie

    (Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia)

  • Jamie Rossjohn

    (School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia
    Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK)

  • James McCluskey

    (University of Melbourne, Parkville, Victoria 3010, Australia)

Abstract

Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.

Suggested Citation

  • Lars Kjer-Nielsen & Onisha Patel & Alexandra J. Corbett & Jérôme Le Nours & Bronwyn Meehan & Ligong Liu & Mugdha Bhati & Zhenjun Chen & Lyudmila Kostenko & Rangsima Reantragoon & Nicholas A. Williamso, 2012. "MR1 presents microbial vitamin B metabolites to MAIT cells," Nature, Nature, vol. 491(7426), pages 717-723, November.
    • Handle: RePEc:nat:nature:v:491:y:2012:i:7426:d:10.1038_nature11605
    DOI: 10.1038/nature11605
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    Cited by:

    1. Matthew P. Mulè & Andrew J. Martins & John S. Tsang, 2022. "Normalizing and denoising protein expression data from droplet-based single cell profiling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Robert Z Harms & Kristina M Lorenzo & Kevin P Corley & Monina S Cabrera & Nora E Sarvetnick, 2015. "Altered CD161bright CD8+ Mucosal Associated Invariant T (MAIT)-Like Cell Dynamics and Increased Differentiation States among Juvenile Type 1 Diabetics," PLOS ONE, Public Library of Science, vol. 10(1), pages 1-21, January.
    3. Ann-Christin Gnirck & Marie-Sophie Philipp & Alex Waterhölter & Malte Wunderlich & Nikhat Shaikh & Virginia Adamiak & Lena Henneken & Tobias Kautz & Tingting Xiong & Daniela Klaus & Pascal Tomczyk & M, 2023. "Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Lauren Stern & Helen M. McGuire & Selmir Avdic & Barbara Fazekas de St Groth & David Gottlieb & Allison Abendroth & Emily Blyth & Barry Slobedman, 2022. "Immunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Morgane Mabire & Pushpa Hegde & Adel Hammoutene & Jinghong Wan & Charles Caër & Rola Al Sayegh & Mathilde Cadoux & Manon Allaire & Emmanuel Weiss & Tristan Thibault-Sogorb & Olivier Lantz & Michèle Go, 2023. "MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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