Major Histocompatibility Complex, class I-related protein (MR1) (MR1)

Major Histocompatibility Complex, class I-related protein (MR1) is a highly conserved, non-polymorphic antigen-presenting molecule that plays a pivotal role in the innate-like immune system (UniProt P17693). Unlike classical MHC molecules that present peptides or CD1 molecules that present lipids, MR1 specifically captures and presents small-molecule metabolites, most notably those derived from the riboflavin (vitamin B2) biosynthetic pathway (Corbett et al., 2014, Nature). These ligands, such as 5-OP-RU, are recognized by the T-cell receptors of Mucosal-Associated Invariant T (MAIT) cells, triggering a rapid immune response characterized by cytokine production and cytotoxicity (Kjer-Nielsen et al., 2012, Nature). Because the riboflavin pathway is present in many bacteria and fungi but absent in mammals, MR1 serves as a critical sensor for microbial infection. Therapeutically, MR1 and its ligands are being investigated as targets for novel vaccines, cancer immunotherapies, and treatments for autoimmune diseases, where modulating MAIT cell activity can either enhance pathogen clearance or suppress harmful inflammation (Keller et al., 2017, Nature Reviews Immunology).

Other names

MHC class I-related proteinMR1Class I-related antigen MR1MR1-restricted antigensMAIT cell ligandsRiboflavin-derived metabolites

MR1 ligands bind within the A' pocket of the MR1 molecule, often forming a covalent Schiff base bond with the Lys43 residue. This binding stabilizes the MR1 protein, allowing it to egress from the endoplasmic reticulum to the cell surface, where the MR1-ligand complex is recognized by the T-cell receptor (TCR) of Mucosal-Associated Invariant T (MAIT) cells, leading to their activation and effector function.