title: Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk.
abstract: The molecular mechanisms involved in the full activation of innate immunity achieved through Toll-like receptors (TLRs) remain to be fully elucidated. In addition to their classical antigen-presenting function, major histocompatibility complex (MHC) class II molecules might mediate reverse signaling. Here we report that deficiency in MHC class II attenuated the TLR-triggered production of proinflammatory cytokines and type I interferon in macrophages and dendritic cells, which protected mice from endotoxin shock. Intracellular MHC class II molecules interacted with the tyrosine kinase Btk via the costimulatory molecule CD40 and maintained Btk activation, but cell surface MHC class II molecules did not. Then, Btk interacted with the adaptor molecules MyD88 and TRIF and thereby promoted TLR signaling. Therefore, intracellular MHC class II molecules can act as adaptors, promoting full activation of TLR-triggered innate immune responses.
authors: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors: Xingguang
authors: X
authors: Liu
authors: Zhenzhen
authors: Z
authors: Zhan
authors: Dong
authors: D
authors: Li
authors: Li
authors: L
authors: Xu
authors: Feng
authors: F
authors: Ma
authors: Peng
authors: P
authors: Zhang
authors: Hangping
authors: H
authors: Yao
authors: Xuetao
authors: X
authors: Cao
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004789:Enzyme Activation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000077329:Agammaglobulinaemia Tyrosine Kinase; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D053594:Myeloid Differentiation Factor 88; D011505:Protein-Tyrosine Kinases; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse