Epitopes described in "MR1 presents microbial vitamin B metabolites to MAIT cells."

Article Authors: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; James McCluskey
Article Title:MR1 presents microbial vitamin B metabolites to MAIT cells.
Reference Detail
Reference ID:1025184
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.
Reference Type:Literature
PubMed ID:23051753
Journal Volume:491
Article Pages:717-23
Journal ISSN:1476-4687
Article Chemical List:Histocompatibility Antigens;Histocompatibility Antigens Class I;Ligands;MR1 protein, human;Pterins;beta 2-Microglobulin;Folic Acid
Article MeSH List:Antigen Presentation; Bacterial Infections(immunology; microbiology); Binding Sites; Cell Line; Crystallography, X-Ray; Folic Acid(chemistry; immunology; metabolism); Histocompatibility Antigens(chemistry; immunology); Histocompatibility Antigens Class I(chemistry; immunology; metabolism); Humans; Immunologic Surveillance(immunology); Jurkat Cells; Ligands; Lymphocyte Activation; Models, Molecular; Protein Refolding(drug effects); Pterins(chemistry; immunology; metabolism; pharmacology); Salmonella(immunology; metabolism); Salmonella Infections(immunology; microbiology); Static Electricity; T-Lymphocytes(immunology); beta 2-Microglobulin(immunology; metabolism)
Curation Last Updated:2016-05-11 20:11:31