title: MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.
abstract: In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, the RING-CH ubiquitin E3 ligase, membrane-associated RING-CH I (MARCH I), promotes the ubiquitination of the HLA-DR beta-chain. Thus, in nonactivated DCs, MARCH I induces the surface internalization of mature HLA-DR complexes, therefore reducing their stability and levels. We further demonstrate that the maturation-dependent down-regulation of MARCH I is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. MARCH I is, therefore, a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.
authors.forename: Aude
authors.initials: A
authors.lastname: De Gassart
authors.forename: Voahirana
authors.initials: V
authors.lastname: Camosseto
authors.forename: Jacques
authors.initials: J
authors.lastname: Thibodeau
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceppi
authors.forename: Nadia
authors.initials: N
authors.lastname: Catalan
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
authors.forename: Evelina
authors.initials: E
authors.lastname: Gatti
mesh_terms: D000954:Antigens, Surface; D001692:Biological Transport; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics*; D004705:Endocytosis; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D000954:Antigens, Surface; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; C528121:MARCHF1 protein, human; D044767:Ubiquitin-Protein Ligases