MR1 presents microbial vitamin B metabolites to MAIT cells

Kjer-Nielsen, Lars, Patel, Onisha, Corbett, Alexandra J., Le Nours, Jerome, Meehan, Bronwyn, Liu, Ligong, Bhati, Mugdha, Chen, Zhenjun, Kostenko, Lyudmila, Reantragoon, Rangsima, Williamson, Nicholas A., Purcell, Anthony W., Dudek, Nadine L., McConville, Malcolm J., O'Hair, Richard A. J., Khairallah, George N., Godfrey, Dale I., Fairlie, David P., Rossjohn, Jamie and McCluskey, James (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature, 491 7426: 717-725. doi:10.1038/nature11605

Author Kjer-Nielsen, Lars
Patel, Onisha
Corbett, Alexandra J.
Le Nours, Jerome
Meehan, Bronwyn
Liu, Ligong
Bhati, Mugdha
Chen, Zhenjun
Kostenko, Lyudmila
Reantragoon, Rangsima
Williamson, Nicholas A.
Purcell, Anthony W.
Dudek, Nadine L.
McConville, Malcolm J.
O'Hair, Richard A. J.
Khairallah, George N.
Godfrey, Dale I.
Fairlie, David P.
Rossjohn, Jamie
McCluskey, James
Title MR1 presents microbial vitamin B metabolites to MAIT cells
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2012-10-10
Year available 2012
Sub-type Article (original research)
DOI 10.1038/nature11605
Open Access Status Not Open Access
Volume 491
Issue 7426
Start page 717
End page 725
Total pages 9
Place of publication London, United Kingdom
Publisher Nature
Language eng
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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Created: Wed, 14 Nov 2012, 22:42:17 EST by Susan Allen on behalf of Institute for Molecular Bioscience