MR1 (in Mouse and Man)
MR1 (major histocompatibility complex (MHC)-related protein 1) is a nonpolymorphic class Ib antigen presenting molecule recognized by the innate-like mucosal-associated invariant T cell subset. MR1 is highly conserved across all mammals, implying an essential role in host defense. It presents nonprotein antigens which include precursors and derivatives from highly conserved microbial biosynthetic pathways of riboflavin and folic acid metabolism. MR1 was identified in 1995 by degenerate PCR on human chromosome 1q25. MR1 is ubiquitously expressed across tissues, at relatively high abundance, but with virtually no detectable constitutive surface expression. MR1 has a standard MHC-I fold, with a1 and a2 helices forming an exposed antigen-binding cleft, held open by several bulky side chains, with a b-sheet floor. MR1 ligands include formylpterins, naturally occurring photodegradation products of folic acid (vitamin B9), and ribityllumazines, precursors and derivatives of vitamin B2. MR1 predominantly exists in the late endoplasmic reticulum (ER), trafficking through the late endosomal and lysosomal compartments where it binds ligand, facilitated by chaperones from the MHC-II pathway: the invariant chain and HLA-DM. Diseases associated with MR1 deficiencies or polymorphisms are yet to be described, but are likely to produce predisposition to multisystem invasive infections, or chronic autoimmune inflammatory diseases.