MR1

MAIT (mucosal-associated invariant T-cells) lymphocytes represent a small population of T-cells primarily found in the gut. The protein encoded by this gene is an antigen-presenting molecule that presents metabolites of microbial vitamin B to MAITs. This presentation may activate the MAITs to regulate the amounts of specific types of bacteria in the gut. Several transcript variants encoding different isoforms have been found for this gene, and a pseudogene of it has been detected about 36 kbp upstream on the same chromosome.

major histocompatibility complex, class I-related

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 (PubMed:23051753, PubMed:26795251, PubMed:12794138, PubMed:19416870, PubMed:22692454, PubMed:23846752).

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 (PubMed:26795251, PubMed:24695216, PubMed:20581831).

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 (PubMed:24695216).

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 (PubMed:27527800, PubMed:31113973).

Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (PubMed:24695216, PubMed:27527800, PubMed:23846752).

During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (By similarity).

Acts as an immune sensor of cancer cell metabolome (PubMed:31959982).

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 (PubMed:31959982).

Antigen processing and presentation of exogenous antigen Source: UniProtKB
Antigen processing and presentation of peptide antigen via MHC class I Source: UniProtKB-KW
Defense response to Gram-negative bacterium Source: UniProtKB
Defense response to Gram-positive bacterium Source: UniProtKB
Immune response Source: ProtInc
Innate immune response Source: UniProtKB-KW
Positive regulation of T cell mediated cytotoxicity directed against tumor cell target Source: UniProtKB
T cell differentiation in thymus Source: UniProtKB

Plasma membrane
Cell membrane
Golgi apparatus
Golgi apparatus membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Endosome
Early endosome membrane
Late endosome membrane
Note: In the absence of antigen remains within the endoplasmic reticulum where it acts as a metabolite sensor. Antigen binding triggers trafficking of the ternary complex to the plasma membrane. After presentation, most of these complexes are rapidly internalized and degraded via endocytosis. A 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 reticulum.
Isoform 1:
Plasma membrane
Cell membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Isoform 3:
Plasma membrane
Cell membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Note: The larger proportion remains in the ER in an immature state. The subset that reach cell surface does it through a B2M-independent pathway.
Isoform 4:
Secreted

Extracellular: 23-302
Helical: 303-323
Cytoplasmic: 324-341

N-glycosylated.