MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.
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.
De Gassart
Aude
A
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.
Camosseto
Voahirana
V
Thibodeau
Jacques
J
Ceppi
Maurizio
M
Catalan
Nadia
N
Pierre
Philippe
P
Gatti
Evelina
E
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*
D000954:Antigens, Surface; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; C528121:MARCHF1 protein, human; D044767:Ubiquitin-Protein Ligases