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MR1 uses an endocytic pathway to activate mucosal‐associated invariant T cells
Author(s) -
Huang Shouxiong,
Gilfillan Susan,
Kim Sojung,
Thompson Bruce,
Wang Xiaoli,
Fremont Daved,
Lantz Olivier,
Hansen Ted
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.11
Subject(s) - endosome , endocytic cycle , microbiology and biotechnology , t cell receptor , biology , population , natural killer t cell , t cell , cell , immunology , intracellular , endocytosis , immune system , biochemistry , demography , sociology
Mucosal Associated Invariant T (MAIT) cells are an “innate” T cell population expressing an invariant TCRα chain, mVαl9 in mice and hVα7.2 in humans. Strikingly similar to CD 1d‐restricted i NKT cells, MAIT cells have a memory phenotype and rapidly release IFN‐γ, IL‐4, 5, and 10 upon TCR ligation. Interestingly, MAIT cells are also restricted by an MHC class I like molecule, MR1. But, unlike i NKT cells, MAIT cells require B cells and gut commensal flora for development and/or expansion. Although the ligand presented by MR1 is unknown, evidence strongly suggests that MAIT cell activation is ligand‐dependent. Here we demonstrate that MR1 antigen presentation is not affected by either the proteasome or the class I chaperones. However, the class II chaperone invariant chain, Ii, physically associates with MR1 and promotes its endosomal trafficking. Functionally, MAIT cell activation is enhanced by Ii overexpression but strikingly diminished by silencing endogenous Ii. Furthermore, confocal microscopy confirms localization of MR1 in late endosomes and inhibiting the acidification of these compartments reduces MR1 surface expression and ablates MAIT cell activation. These data indicate that MR1 traffics through endocytic compartments, thereby allowing MAIT cells to potentially sample both endocytosed and endogenous antigens.