MAIT cells and MR1-antigen recognition

- MR1 presents vitamin B precursors and metabolites to MAIT cells.
- The MR1-restricted T cell repertoire is diverse.
- MAIT TCR heterogeneity can impact on MR1-antigen responsiveness.
- MR1 presents drugs and drug-like molecules.

Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules. With mounting evidence demonstrating their roles in immunity and pathology, understanding the MAIT-MR1-antigen axis may have profound implications for human diseases.