MR1 presents microbial vitamin B metabolites to MAIT cells
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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Favorable taxa also showed higher abundance of flavin and riboflavin metabolism genes.
“We also observed increased abundance of genes encoding flavin and riboflavin metabolism, byproducts of which can be presented by MR1 and recognized by mucosal-associated invariant T cells11,44, which we showed are activated in PD-1-responsive patients after FMT11.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [44]
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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
- ORCID
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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