MR1: a multi-faceted metabolite sensor for T cell activation.

The major histocompatibility complex class I-related molecule MR1 captures and presents small metabolites to MR1-restricted T cells including Mucosal Associated Invariant T (MAIT) cells. The first MR1 ligands discovered were intermediates of microbial riboflavin synthesis, antigens presented to alert inflammatory MAIT cells to bacterial infection. Recent advances have expanded the range of MR1 ligands to include extracellular metabolites released by the commensal microbiome, and yet undefined antigens presented by cancer cells to mediate MR1-dependent anti-tumor activity. MR1 thus exhibits a multifaceted ability to display a diverse range of ligands for immune surveillance in a variety of contexts. The mechanisms of antigen presentation by MR1 are of central importance to understanding metabolite-mediated immune homeostasis, immunity to infection and tumor surveillance.