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Recognition of vitamin B metabolites by mucosal-associated invariant T cells

Patel, O., Kjer-Nielsen, L., Le Nours, J., Eckle, S., Birkinshaw, R., Beddoe, T., Corbett, A., Liu, L., Miles, John James, Meehan, B., Reantragoon, R., Sandoval-Romero, M., Sullivan, L., Brooks, A., Chen, Z., Fairlie, D., McCluskey, J. and Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 2013. Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nature Communications 4 (2142) 10.1038/ncomms3142

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Abstract

The mucosal-associated invariant T-cell antigen receptor (MAIT TCR) recognizes MR1 presenting vitamin B metabolites. Here we describe the structures of a human MAIT TCR in complex with human MR1 presenting a non-stimulatory ligand derived from folic acid and an agonist ligand derived from a riboflavin metabolite. For both vitamin B antigens, the MAIT TCR docks in a conserved manner above MR1, thus acting as an innate-like pattern recognition receptor. The invariant MAIT TCR α-chain usage is attributable to MR1-mediated interactions that prise open the MR1 cleft to allow contact with the vitamin B metabolite. Although the non-stimulatory antigen does not contact the MAIT TCR, the stimulatory antigen does. This results in a higher affinity of the MAIT TCR for a stimulatory antigen in comparison with a non-stimulatory antigen. We formally demonstrate a structural basis for MAIT TCR recognition of vitamin B metabolites, while illuminating how TCRs recognize microbial metabolic signatures.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Crystallography, X-Ray; Escherichia coli; Folic Acid; Histocompatibility Antigens Class I; Humans; Intestinal Mucosa; Jurkat Cells; Molecular Docking Simulation; Protein Interaction Domains and Motifs; Protein Refolding; Receptors, Antigen, T-Cell, alpha-beta; Recombinant Proteins; Riboflavin; T-Lymphocytes
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of Acceptance: 13 June 2013
Last Modified: 10 Jun 2023 01:10
URI: https://orca.cardiff.ac.uk/id/eprint/75662

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