MR1 presents microbial vitamin B metabolites to MAIT cells
Lars Kjer-Nielsen, Onisha Patel, Alexandra J Corbett, Jerome 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 AJ O'Hair, George N Khairallah, Dale I Godfrey, David P Fairlie, Jamie Rossjohn, James McCluskey
Nature | NATURE PUBLISHING GROUP | Published : 2012
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..View full abstract
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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.