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 |
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 |
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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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