Microbiology & Immunology - Research Publications

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Author: Corbett, Alexandra × Subject: bacterial infections/immunology ×

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    MR1 presents microbial vitamin B metabolites to MAIT cells
    Kjer-Nielsen, L ; Patel, O ; Corbett, AJ ; Le Nours, J ; Meehan, B ; Liu, L ; Bhati, M ; Chen, Z ; Kostenko, L ; Reantragoon, R ; Williamson, NA ; Purcell, AW ; Dudek, NL ; McConville, MJ ; O'Hair, RAJ ; Khairallah, GN ; Godfrey, DI ; Fairlie, DP ; Rossjohn, J ; McCluskey, J (NATURE PUBLISHING GROUP, 2012-11-29)
    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.