MHC class I-related protein 1 (MR1)

MHC class I-related protein 1 (MR1) is a highly conserved non-classical MHC class Ib molecule that plays a critical role in the innate-like immune system. Unlike traditional MHC molecules that present peptide or lipid antigens, MR1 is unique in its ability to bind and present small molecule metabolites, specifically those derived from the riboflavin (vitamin B2) biosynthetic pathway found in many bacteria and fungi. Upon binding these ligands, MR1 translocates to the cell surface to activate mucosal-associated invariant T (MAIT) cells, which subsequently release pro-inflammatory cytokines and exert cytotoxic functions to control microbial infections (Corbett et al., 2014, Nature; UniProt Q95460). Beyond its role in infectious disease, MR1 has emerged as a promising target in oncology and immunotherapy. Recent research has identified MR1-restricted T cells that can recognize and kill a wide range of human cancer cells in a metabolite-dependent but MHC-independent manner, suggesting a pan-cancer therapeutic potential (Crowther et al., 2020, Nature Immunology). Pharmacological modulation of MR1 using synthetic ligands like 5-OP-RU (an agonist) or Ac-6-FP (an antagonist) is being actively explored to either enhance anti-tumor immunity or suppress pathological inflammation in autoimmune diseases. Because MR1 is monomorphic and highly conserved across the human population, therapies targeting this protein do not require patient-specific HLA matching, offering a significant advantage for 'off-the-shelf' cellular and molecular therapeutics.

Other names

Major histocompatibility complex class I-related gene proteinClass I-like antigen MR1HLALS

MR1 captures small molecule metabolites derived from microbial vitamin B2 (riboflavin) synthesis or folate pathways within the endoplasmic reticulum. These MR1-ligand complexes then translocate to the cell surface, where they are recognized by the T-cell receptors (TCRs) of mucosal-associated invariant T (MAIT) cells, leading to MAIT cell activation and cytokine production.