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The Toll‐like receptor 9 signalling pathway regulates MR 1‐mediated bacterial antigen presentation in B cells
Author(s) -
Liu Jianyun,
Brutkiewicz Randy R.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12759
Subject(s) - tlr9 , microbiology and biotechnology , antigen presentation , endosome , cpg oligodeoxynucleotide , biology , antigen , endoplasmic reticulum , antigen presenting cell , antigen processing , t cell , immune system , immunology , gene expression , gene , biochemistry , intracellular , dna methylation
Summary Mucosal‐associated invariant T ( MAIT ) cells are conserved T cells that express a semi‐invariant T ‐cell receptor (V α 7.2 in humans and V α 19 in mice). The development of MAIT cells requires the antigen‐presenting MHC ‐related protein 1 ( MR 1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR 1 molecules and their loading with bacterial antigen in antigen‐presenting cells are largely unknown. We have found that treating B cells with the Toll‐like receptor 9 ( TLR 9) agonist CpG increases MR 1 surface expression. Interestingly, activation of TLR 9 by CpG‐A (but not CpG‐B) enhances MR 1 surface expression. This is limited to B cells and not other types of cells such as monocytes, T or natural killer cells. Knocking‐down TLR 9 expression by short hairpin RNA reduces MR 1 surface expression and MR 1‐mediated bacterial antigen presentation. CpG‐A triggers early endosomal TLR 9 activation, whereas CpG‐B is responsible for late endosomal/lysosomal activation of TLR 9. Consistently, blocking endoplasmic reticulum to Golgi protein transport, rather than lysosomal acidification, suppressed MR 1 antigen presentation. Overall, our results indicate that early endosomal TLR 9 activation is important for MR 1‐mediated bacterial antigen presentation.