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

Patel, Onisha, Kjer-Nielsen, Lars, Le Nours, Jérôme, Eckle, Sidonia B.G., Birkinshaw, Richard, Beddoe, Travis, Corbett, Alexandra J., Liu, Ligong, Miles, John, Meehan, Bronwyn, Reantragoon, Rangsima, Sandoval-Romero, Maria L., Sullivan, Lucy C., Brooks, Andrew G., Chen, Zhenjun, Fairlie, David P., McCluskey, James, and Rossjohn, Jamie (2013) Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nature Communications, 4. pp. 1-9.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: http://dx.doi.org/10.1038/ncomms3142
 
124
4


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 ID: 45064
Item Type: Article (Research - C1)
ISSN: 2041-1723
Funders: National Health and Medical Research Council of Australia (NHMRC), Australian Research Council (ARC), Pfizer Australia Research Fellowship (PARF)
Date Deposited: 10 Aug 2016 01:56
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
Downloads: Total: 4
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page