MR1B, a natural spliced isoform of the MHC-related 1 protein, is expressed as homodimers at the cell surface and activates MAIT cells

作者:Lion Julien; Debuysscher Veronique; Wlodarczyk Anais; Hodroge Ahmed; Serriari Nacer Eddine; Choteau Ludivine; Ouled haddou Hakim; Plistat Maggy; Lassoued Kaiss; Lantz Olivier; Treiner Emmanuel*
来源:European Journal of Immunology, 2013, 43(5): 1363-1373.
DOI:10.1002/eji.201242461

摘要

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 3 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 2-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.

  • 出版日期2013-4