title: Molecular mechanism and cellular function of MHCII ubiquitination.
abstract: The major histocompatibility complex class II (MHCII) is ubiquitinated via the evolutionarily conserved lysine in the cytoplasmic tail of the β chain in dendritic cells (DCs) and B cells. The ubiquitination is mediated by the membrane-associated RING-CH1 (MARCH1) ubiquitin ligase although it can be also mediated by the homologous ligase MARCH8 in model cell lines. The ubiquitination promotes MHCII endocytosis and lysosomal sorting that results in a reduction in the level of MHCII at cell surface. Functionally, MHCII ubiquitination serves as a means by which DCs suppress MHCII expression and reduce antigen presentation in response to the immune regulatory cytokine interleukin-10 (IL-10) and regulatory T cells. Recently, additional roles of MHCII ubiquitination have emerged. MHCII ubiquitination promoted DC production of inflammatory cytokines in response to the Toll-like receptor ligands. It also potentiated DC ability to activate antigen-specific naive CD4(+) T cells while limiting the amount of antigens presented at cell surface. Similarly, MHCII ubiquitination promoted DC activation of CD4(+) thymocytes supporting regulatory T-cell development independent of its effect of limiting antigen presentation. Thus, ubiquitination appears to confer MHCII a function independent of presenting antigens by a mechanism yet to be identified.
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Jaehak
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Jeoung-Sook
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D054875:Ubiquitination
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II
keywords: MARCH; MHCII; TLR; dendritic cell; regulatory T cell; ubiquitination