Besides their classical function in antigen presentation, MHC class I molecules have now been shown to negatively regulate Toll-like receptor (TLR)-triggered inflammatory responses. Xu et al. first noted that MHC class I-deficient mice produced markedly more pro-inflammatory cytokines in response to TLR ligands and were more sensitive to lethal challenge with lipopolysaccharide (LPS) than control mice. Interaction of MHC class I-expressing macrophages with CD8+ T cells led to the suppression of TLR-triggered cytokine production. Further analyses revealed that the intracellular tyrosine residues in membrane MHC class I molecules are phosphorylated by the kinase SRC after LPS stimulation of macrophages, and this allows the recruitment of the kinase FPS to the MHC class I molecules. FPS mediated the suppressive effect by activating the phosphatase SHP2, which interferes with TLR signalling mediated by TNFR-associated factor 6 (TRAF6).
ORIGINAL RESEARCH PAPER
Xu, S. et al. Constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps–SHP-2 pathway. Nature Immunol. 22 Apr 2012 (doi:10.1038/ni.2283)
Rights and permissions
About this article
Cite this article
Bird, L. MHC class I as a negative regulator of TLR signalling. Nat Rev Immunol 12, 401 (2012). https://doi.org/10.1038/nri3243
Published:
Issue Date:
DOI: https://doi.org/10.1038/nri3243