MR1 presents microbial vitamin B metabolites to MAIT cells

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. Williamson, Anthony W. Purcell, Nadine L. Dudek, Malcolm J. McConville, Richard A. J. O’Hair, George N. Khairallah, Dale I. Godfrey, David P. Fairlie, Jamie Rossjohn () and James McCluskey ()
Additional contact information
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
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
Nadine L. Dudek: School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, 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
James McCluskey: University of Melbourne, Parkville, Victoria 3010, Australia

Nature, 2012, vol. 491, issue 7426, 717-723

Abstract: 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.

Date: 2012
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DOI: 10.1038/nature11605

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