title: MR1B, a natural spliced isoform of the MHC-related 1 protein, is expressed as homodimers at the cell surface and activates MAIT cells.
abstract: The MHC-related 1 (MR1) protein is a monomorphic, evolutionarily conserved MHC class I-like molecule, which is necessary for the development and functions of mucosal-associated invariant T (MAIT) cells, a new subset of innate-like lymphocytes. Multiple isoforms of the MR1 gene are naturally transcribed, but only the full-length MR1A has been analyzed so far. Using transfected cell lines expressing an alternative spliced transcript, MR1B, characterized by the absence of the α3 extracellular domain, we show that MR1B is transcribed and glycosylated but remains in an immature (endoglycosidase H-sensitive) state. MR1B mostly accumulates in the ER, without interacting with proteins of the peptide-loading complex such as tapasin. Interestingly, it is nevertheless found expressed at the cell surface, independently of β2-microglobulin, in a homodimeric form. MR1B is functional as its overexpression induces MAIT cell activation in vitro in the presence of bacteria. Altogether, these data show that MR1B displays several remarkable features, and probably plays a physiological role complementary to MR1A with respect to MAIT cell development and/or function.
authors: Avenir Group Inserm UMR925, Amiens, France.
authors: Julien
authors: J
authors: Lion
authors: Veronique
authors: V
authors: Debuysscher
authors: Anais
authors: A
authors: Wlodarczyk
authors: Ahmed
authors: A
authors: Hodroge
authors: Nacer-Eddine
authors: NE
authors: Serriari
authors: Ludivine
authors: L
authors: Choteau
authors: Hakim
authors: H
authors: Ouled-haddou
authors: Maggy
authors: M
authors: Plistat
authors: Kaiss
authors: K
authors: Lassoued
authors: Olivier
authors: O
authors: Lantz
authors: Emmanuel
authors: E
authors: Treiner
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology*; D019281:Dimerization; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D010957:Plasmids; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D020033:Protein Isoforms