Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk

Xingguang Liu; Zhenzhen Zhan; Dong Li; Li Xu; Feng Ma; Peng Zhang; Hangping Yao; Xuetao Cao

doi:10.1038/ni.2015

Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk

Nat Immunol. 2011 May;12(5):416-24. doi: 10.1038/ni.2015. Epub 2011 Mar 27.

Authors

Xingguang Liu¹, Zhenzhen Zhan, Dong Li, Li Xu, Feng Ma, Peng Zhang, Hangping Yao, Xuetao Cao

Affiliation

¹ National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.

PMID: 21441935
DOI: 10.1038/ni.2015

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Vesicular Transport / immunology
Agammaglobulinaemia Tyrosine Kinase
Animals
Antigen-Presenting Cells / enzymology
Antigen-Presenting Cells / immunology
CD40 Antigens / immunology
Cell Line
Cytokines / blood
Cytokines / immunology
Enzyme Activation
Histocompatibility Antigens Class II / immunology*
Immunity, Innate / immunology*
Immunoblotting
Interferon-gamma / blood
Interferon-gamma / immunology
Kaplan-Meier Estimate
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 / immunology
Protein-Tyrosine Kinases / immunology
Protein-Tyrosine Kinases / metabolism*
Sepsis / immunology
Specific Pathogen-Free Organisms
Toll-Like Receptors / immunology*

Substances

Adaptor Proteins, Vesicular Transport
CD40 Antigens
Cytokines
Histocompatibility Antigens Class II
Myd88 protein, mouse
Myeloid Differentiation Factor 88
TICAM-1 protein, mouse
Toll-Like Receptors
Interferon-gamma
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase