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MR1 presents microbial vitamin B metabolites to MAIT cells
- Source :
- Nature. 491:717-723
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
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.
- Subjects :
- Models, Molecular
T-Lymphocytes
Static Electricity
Population
Antigen presentation
CD1
chemical and pharmacologic phenomena
Crystallography, X-Ray
Ligands
Lymphocyte Activation
Major histocompatibility complex
Protein Refolding
Cell Line
Minor Histocompatibility Antigens
Jurkat Cells
chemistry.chemical_compound
Folic Acid
Immune system
Antigen
Salmonella
Histocompatibility Antigens
MHC class I
Humans
Pterin
education
Immunologic Surveillance
Antigen Presentation
education.field_of_study
Binding Sites
Multidisciplinary
biology
Histocompatibility Antigens Class I
Bacterial Infections
Research Highlight
Pterins
Biochemistry
chemistry
Salmonella Infections
biology.protein
beta 2-Microglobulin
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 491
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....7ab17c25e2911cbd988bcdb9d1da2fdd