MR1
Domain
The alpha-1 domain is a structural part of antigen-binding cleft.
The alpha-2 domain is a structural part of antigen-binding cleft.
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 (PubMed:12794138, PubMed:19416870, PubMed:22692454, PubMed:23051753, PubMed:23846752, PubMed:26795251). 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:20581831, PubMed:24695216, PubMed:26795251). 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:23846752, PubMed:24695216, PubMed:27527800). 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).
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the MHC class I family.
Tissue Specificity
Ubiquitous (PubMed:7624800, PubMed:9780177). Low expression is detected in peripheral blood B cells, T cells, monocytes and in bronchial epithelial cells (at protein level) (PubMed:27043408). Expressed in plasmablasts or plasma B cells in the lamina propria of ileum, appendix and colon (at protein level) (PubMed:19760593). Highly expressed on a subset of CD45-positive CD3-positive thymocytes (at protein level) (PubMed:22692454).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum membrane
- Single-pass type I membrane protein
- Golgi apparatus membrane
- Single-pass type I membrane protein
- Early endosome membrane
- Single-pass type I membrane protein
- Late endosome membrane
- Single-pass type I membrane protein
- 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
- Cell membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Isoform 3
- Cell membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- 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
Alternative names
Major histocompatibility complex class I-related gene protein, MHC class I-related gene protein, Class I histocompatibility antigen-like protein, MR1