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.

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Protein Data Bank

Data deposits

The atomic coordinates and structure factors for theMR1–antigen complex were deposited in the Protein Data Bank (PDB) under accession code 4GUP.


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We thank R. Strugnell, T. Stinear, T. Mulhern, P. O’Donnell, J. Pyke, T. Rupasinghe, D. L. Tull, J. Ralton, L. Foster, S. H. Ramarathinam, M. Bharadwaj, D. Pellicci and K. Wun for discussions and technical advice, T. Hansen for the anti-MR1 monoclonal antibody and the staff of the Australian Synchrotron for assistance with data collection. This research was supported by the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council. O.P. was supported by an ARC Future Fellowship; A.W.P. by an NHMRC Senior Research Fellowship; M.J.M. by a NHMRC Principal Research Fellowship; D.I.G. and D.P.F. were supported by NHMRC Senior Principal Research Fellowships; J.R. was supported by an NHMRC Australia Fellowship.

Author information

Author notes

    • Jamie Rossjohn
    •  & James McCluskey

    These authors contributed equally to this work.


  1. Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia

    • Lars Kjer-Nielsen
    • , Alexandra J. Corbett
    • , Bronwyn Meehan
    • , Zhenjun Chen
    • , Lyudmila Kostenko
    • , Rangsima Reantragoon
    • , Dale I. Godfrey
    •  & James McCluskey
  2. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia

    • Onisha Patel
    • , Jérôme Le Nours
    • , Mugdha Bhati
    • , Anthony W. Purcell
    • , Nadine L. Dudek
    •  & Jamie Rossjohn
  3. Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia

    • Jérôme Le Nours
    •  & Jamie Rossjohn
  4. Division of Chemistry & Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia

    • Ligong Liu
    •  & David P. Fairlie
  5. Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, Metabolomics Australia, University of Melbourne, Parkville, Victoria 3010, Australia

    • Nicholas A. Williamson
    • , Anthony W. Purcell
    • , Nadine L. Dudek
    •  & Malcolm J. McConville
  6. 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

    • Richard A. J. O’Hair
    •  & George N. Khairallah
  7. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK

    • Jamie Rossjohn


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L.K.-N. identified the MR1 and MAIT ligands, undertook analysis, performed experiments and contributed to manuscript preparation. O.P. and J.L.N. solved the structure of MR1, conducted analyses and contributed to manuscript preparation. B.M., A.J.C., M.B., A.J.C., L.K., R.R., N.A.W., A.W.P., N.L.D., M.J.M., R.A.J.O.’H., G.N.K. and D.I.G. performed experiments and/or analysed data and/or provided intellectual input or helped to write the manuscript. L.L. and D.P.F. synthesized and devised the MAIT-cell activating ligands and contributed to writing the manuscript. J.M. and J.R. co-led the investigation and contributed to design and interpretation of data, project management, and writing of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jamie Rossjohn or James McCluskey.

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