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. 2142. pp. 1-9.

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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.

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