• 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.
• Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
• Nature. 2012 Nov 29; 491 (7426): 717-23.

AbstractAntigen-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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