Major histocompatibility complex class I-related protein (MR1) (MR1)

The Major histocompatibility complex class I-related protein (MR1) is a highly conserved, non-classical MHC molecule that serves as the central mediator of the MR1–MAIT cell axis (UniProt Q95460). Unlike classical MHC molecules that present peptide antigens, MR1 is uniquely specialized to present small-molecule metabolites, primarily riboflavin (vitamin B2) derivatives like 5-OP-RU, which are synthesized by a broad range of bacteria and fungi (Nature 2014, 509:585-590). These metabolites are presented to Mucosal-Associated Invariant T (MAIT) cells, which recognize the MR1-ligand complex via their semi-invariant T-cell receptors (TCRs), triggering a rapid and potent immune response (Science 2014, 343:1495-1500). Upon activation, MAIT cells secrete pro-inflammatory cytokines such as IFN-gamma and TNF and exert direct cytotoxic effects on infected or malignant cells. Because MR1 is monomorphic and essentially identical across the human population, it represents a promising target for universal, "off-the-shelf" immunotherapies that bypass the complexities of HLA-matching (Nature Communications 2020, 11:2428). Current therapeutic development focuses on using MR1 ligands to activate MAIT cells for treating infectious diseases and cancer, or employing MR1 antagonists to mitigate MAIT cell-driven inflammation in autoimmune conditions like multiple sclerosis and inflammatory bowel disease (Nature Reviews Immunology 2019, 19:643-657).

Other names

MHC class I-related proteinMR1AHLALSMucosal-associated invariant T-cell axisMR1-MAIT axis

MR1 ligands bind to the antigen-binding cleft of the MR1 protein, inducing a conformational change that allows the protein to move from the endoplasmic reticulum to the cell surface. At the surface, the MR1-ligand complex is recognized by the semi-invariant T-cell receptor (TCR) of MAIT cells, leading to MAIT cell activation, proliferation, and the release of effector cytokines and cytotoxic molecules (Nature 2014, 509:585-590).