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

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 a-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

Lipid and small-molecule display by CD1 and MR1

The antigen-presenting molecules CD1 and MHC class I-related protein (MR1) display lipids and small molecules to T cells. The antigen display platforms in the four CD1 proteins are laterally asymmetrical, so that the T cell receptor (TCR)-binding surfaces are comprised of roofs and portals, rather than the long grooves seen in the MHC antigen-presenting molecules. TCRs can bind CD1 proteins with left-sided or right-sided footprints, creating unexpected modes of antigen recognition. The use of tetramers of human CD1a, CD1b, CD1c or MR1 proteins now allows detailed analysis of the human T cell repertoire, which has revealed new invariant TCRs that bind CD1b molecules and are different from those that define natural killer T cells and mucosal-associated invariant T cells