Protein: Major histocompatibility complex class I-related gene protein (MHC class I-related gene protein) (Class I histocompatibility antigen-like protein) (Q95460)
Organism: Homo sapiens (Human)
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 (By similarity). 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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:12794138, ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:18068122}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein {ECO:0000255}. 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. {ECO:0000269|PubMed:27043408}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:23457030}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23457030}; Single-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:23457030}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23457030}; Single-pass membrane protein {ECO:0000255}. 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. {ECO:0000269|PubMed:23457030}.; SUBCELLULAR LOCATION: [Isoform 4]: Secreted {ECO:0000303|PubMed:9780177}.
Interaction partners:
- Beta-2-microglobulin
- T cell receptor delta variable 1
- T-cell surface glycoprotein CD8 alpha chain
- Tapasin-related protein
- HLA class I histocompatibility antigen, alpha chain E
- HLA class I histocompatibility antigen, C alpha chain
Sequence:
MGELMAFLLPLIIVLMVKHSDSRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHCGVHMVLQVPQESETIPLVMKAVSGSIVLVIVLAGVGVLVWRRRPREQNGAIYLPTPDR