Mucosal‐associated invariant T cell receptor recognition of small molecules presented by MR1

The major histocompatibility complex (MHC) class‐I related molecule MR1 is a monomorphic and evolutionary conserved antigen (Ag)‐presenting molecule that shares the overall architecture of MHC‐I and CD1 proteins. However, in contrast to MHC‐I and the CD1 family that present peptides and lipids, respectively, MR1 specifically presents small organic molecules. During microbial infection of mammalian cells, MR1 captures and presents vitamin B precursors, derived from the microbial biosynthesis of riboflavin, on the surface of antigen‐presenting cells. These MR1‐Ag complexes are recognized by the mucosal‐associated invariant T cell receptor (MAIT TCR), which subsequently leads to MAIT cell activation. Recently, MR1 was shown to trap chemical scaffolds including drug and drug‐like molecules. Here, we review this metabolite Ag‐presenting molecule and further define the key molecular interactions underlying the recognition and reactivity of MAIT TCRs to MR1 in an Ag‐dependent manner.