Cited by 1,351T-cell and B-cell Immunologyvaccines and immunoinformatics approachesImmunotherapy and Immune Responses

MR1 presents microbial vitamin B metabolites to MAIT cells

Kjer-Nielsen, Lars, Patel, Onisha, Corbett, Alexandra J., Le Nours, Jérôme, Meehan, Bronwyn, Liu, Ligong, Bhati, Mugdha, Chen, Zhenjun +12 more·2012·Nature

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.

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Crossref · 10.1038/nature11605

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Authors
Kjer-Nielsen, L., Patel, O., Corbett, A. J., Le Nours, J., Meehan, B., Liu, L., Bhati, M., Chen, Z., Kostenko, L., Reantragoon, R., Williamson, N. A., Purcell, A. W., Dudek, N. L., McConville, M. J., O’Hair, R. A. J., Khairallah, G. N., Godfrey, D. I., Fairlie, D. P., Rossjohn, J., & McCluskey, J.
Affiliations
  • Monash University (AU)
  • The University of Melbourne (AU)
  • The University of Queensland (AU)
  • Australian Research Council (AU)
Corresponding author
  • Rossjohn, Jamie
  • McCluskey, James
Venue
Nature
Published
2012-10-10
Volume
491
Issue
7426
Pages
717-723
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2065252029
Cited by
1,351
References
40
Citations by year
2026: 87 · 2025: 85 · 2024: 88 · 2023: 94 · 2022: 110 · 2021: 128 · 2020: 133 · 2019: 121 · 2018: 120 · 2017: 79 · 2016: 94 · 2015: 83 · 2014: 63 · 2013: 55 · 2012: 9
FWCI
29.26
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
MR1, mucosal-associated invariant T cells, folic acid, riboflavin biosynthesis, antigen presentation, innate-like T cells
MeSH terms
Bacterial Infections, beta 2-Microglobulin, Binding Sites, Cell Line, Folic Acid, Histocompatibility Antigens, Humans, Immunologic Surveillance, Ligands, Lymphocyte Activation, Models, Molecular, Pterins, Salmonella, Salmonella Infections, T-Lymphocytes, Histocompatibility Antigens Class I, Minor Histocompatibility Antigens, Antigen Presentation, Crystallography, X-Ray, Jurkat Cells, Static Electricity, Protein Refolding

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