Mouse Anti-MR1 Recombinant Antibody (CBT2257) (V2LY-0625-LY1710)

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.