IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v491y2012i7426d10.1038_nature11605.html
   My bibliography  Save this article

MR1 presents microbial vitamin B metabolites to MAIT cells

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature11605
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature11605?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Catarina F. Almeida & Benjamin S. Gully & Claerwen M. Jones & Lukasz Kedzierski & Sachith D. Gunasinghe & Michael T. Rice & Richard Berry & Nicholas A. Gherardin & Trang T. Nguyen & Yee-Foong Mok & Jo, 2024. "Direct recognition of an intact foreign protein by an αβ T cell receptor," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:491:y:2012:i:7426:d:10.1038_nature11605. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.