The Toll-like receptor 9 signalling pathway regulates MR1-mediated bacterial antigen presentation in B cells

5 years ago

The Toll-like receptor 9 signalling pathway regulates MR1-mediated bacterial antigen presentation in B cells

Randy R. Brutkiewicz, Jianyun Liu

Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant T-cell receptor (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen-presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 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 (TLR9) agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression. This is limited to B cells and not other types of cells such as monocytes, T or natural killer cells. Knocking-down TLR9 expression by short hairpin RNA reduces MR1 surface expression and MR1-mediated bacterial antigen presentation. CpG-A triggers early endosomal TLR9 activation, whereas CpG-B is responsible for late endosomal/lysosomal activation of TLR9. Consistently, blocking endoplasmic reticulum to Golgi protein transport, rather than lysosomal acidification, suppressed MR1 antigen presentation. Overall, our results indicate that early endosomal TLR9 activation is important for MR1-mediated bacterial antigen presentation. The TLR9 signalling pathway is activated by bacteria. Such signalling in B cells serves as an important contributor to the regulation of bacterial antigen presentation by MR1 to MAIT cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/imm.12759