Publication Date:
2012-10-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- England -- Nature. 2012 Nov 29;491(7426):717-23. doi: 10.1038/nature11605. Epub 2012 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23051753" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
