| Post Translational Modifications | N-glycosylated. |
| Function | Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells. In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TRAV1.2 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers. Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively. May present microbial antigens to various TRAV1-2-negative MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin. Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells. During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora. Acts as an immune sensor of cancer cell metabolome. May present a tumor-specific or -associated metabolite essential for cancer cell survival to a 'pan-cancer' TCR consisting of TRAV38.2-DV8*TRAJ31 alpha chain paired with a TRBV25.1*TRBJ2.3 beta chain on a non-MAIT CD8-positive T cell clone (MC.7.G5), triggering T cell-mediated killing of a wide range of cancer cell types. Allele MR1*01: Presents microbial-derived metabolite 5-OP-RU to semi-invariant TRAV1.2-TRAJ33-TRBV6.1 (A-F7) TCR on MAIT cells. Presents nucleobase carbonyl adducts generated during oxidative stress. Captures M3Ade, a nucleobase adduct composed of one adenine modified by a malondialdehyde trimer, for recognition by MR1-restricted T cell clones expressing a polyclonal TCR repertoire. Displays moderate binding affinity toward tumor-enriched pyridoxal and pyridoxal 5'-phosphate antigens. Allele MR1*04: Presents tumor-enriched metabolite pyridoxal to pan-cancer 7.G5 TCR on T cells enabling preferential recognition of cancer cells. May act as an alloantigen. |
| Protein Name | Major Histocompatibility Complex Class I-Related Protein 1Mhc Class I-Related Protein 1Class I Histocompatibility Antigen-Like Protein |
| Database Links | |
| Cellular Localisation | Cell MembraneSingle-Pass Type I Membrane ProteinEndoplasmic Reticulum MembraneGolgi Apparatus MembraneEarly Endosome MembraneLate Endosome MembraneIn The Absence Of Antigen Remains Within The Endoplasmic Reticulum Where It Acts As A Metabolite SensorAntigen Binding Triggers Trafficking Of The Ternary Complex To The Plasma MembraneAfter PresentationMost Of These Complexes Are Rapidly Internalized And Degraded Via EndocytosisA Small Subset Recycles Via Endosomes Back To The Plasma Membrane And May Thus Acquire And Present New Antigens That Do Not Efficiently Reach The Endoplasmic ReticulumIsoform 1: Cell MembraneSingle-Pass Membrane ProteinIsoform 3: Cell MembraneThe Larger Proportion Remains In The Er In An Immature StateThe Subset That Reach Cell Surface Does It Through A B2m-Independent PathwayIsoform 4: Secreted |
| Alternative Protein Names | Major Histocompatibility Complex Class I-Related Protein 1 proteinMhc Class I-Related Protein 1 proteinClass I Histocompatibility Antigen-Like Protein proteinMR1 protein |
Information sourced from Uniprot.org
