Major histocompatibility complex class I-related gene protein (MHC class I-related gene protein) (Class I histocompatibility antigen-like protein)
1_MGELM 6_ AFLLP 11_ LIIVL 16_ MVKHS 21_ DSRTH 26_ SLRYF 31_ RLGVS 36_ DPIHG 41_ VPEFI 46_ SVGYV 51_ DSHPI 56_ TTYDS 61_ VTRQK 66_ EPRAP 71_ WMAEN 76_ LAPDH 81_ WERYT 86_ QLLRG 91_ WQQMF 96_ KVELK 101_ RLQRH 106_ YNHSG 111_ SHTYQ 116_ RMIGC 121_ ELLED 126_ GSTTG 131_ FLQYA 136_ YDGQD 141_ FLIFN 146_ KDTLS 151_ WLAVD 156_ NVAHT 161_ IKQAW 166_ EANQH 171_ ELLYQ 176_ KNWLE 181_ EECIA 186_ WLKRF 191_ LEYGK 196_ DTLQR 201_ TEPPL 206_ VRVNR 211_ KETFP 216_ GVTAL 221_ FCKAH 226_ GFYPP 231_ EIYMT 236_ WMKNG 241_ EEIVQ 246_ EIDYG 251_ DILPS 256_ GDGTY 261_ QAWAS 266_ IELDP 271_ QSSNL 276_ YSCHV 281_ EHCGV 286_ HMVLQ 291_ VPQES 296_ ETIPL 301_ VMKAV 306_ SGSIV 311_ LVIVL 316_ AGVGV 321_ LVWRR 326_ RPREQ 331_ NGAIY 336_LPTPD
1: 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:19416870, PubMed:23457030, PubMed:22692454, PubMed:23051753, PubMed:24101382, 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:24101382, 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, PubMed:32958637, PubMed:32709702). 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)
2: Allele MR1*01: Presents microbial-derived metabolite 5-OP-RU to semi-invariant TRAV1.2-TRAJ33-TRBV6.1 (A-F7) TCR on MAIT cells (PubMed:39589872). 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 (PubMed:39701104). Displays moderate binding affinity toward tumor-enriched pyridoxal and pyridoxal 5'-phosphate antigens (PubMed:39589872)
3: 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