title: Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells.
abstract: Peptide-MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.
authors.affiliation: Division of Immunobiology, Department of Supramolecular Biology, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishido
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018345:Mice, Knockout; D008822:Mice, Transgenic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D018821:CD18 Antigens; D000949:Histocompatibility Antigens Class II; D018664:Interleukin-12; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: CD86; dendritic cells