Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination.
Dendritic cells (DCs) initiate adaptive immune responses by activating T cells via cognate interactions between MHC-peptide complexes and T cell receptors. In immature DCs, MHC class II is predominantly stored in late endocytic compartments, where it has a short half-life because of degradation. In contrast, mature DCs recruit MHC class II to the plasma membrane. We here demonstrate that in immature DCs, the beta-chain of MHC class II was oligoubiquitinated after proteolytic processing of the associated invariant chain in endosomes and that this modification was required for efficient endocytosis and sorting into luminal vesicles of multivesicular bodies. Ubiquitination of MHC class II was suppressed in lipopolysaccharide-activated DCs. Mutated MHC class II lacking its ubiquitination site was expressed at the plasma membrane, irrespective of DC maturation. Together, these data provide a molecular basis for the regulation of MHC class II-mediated antigen presentation by DCs.
van Niel
Guillaume
G
Faculty of Veterinary Medicine, Department of Biochemistry & Cell Biology, Utrecht University, P.O. Box 80.176, NL-3508 TD, Utrecht, The Netherlands.
Wubbolts
Richard
R
Ten Broeke
Toine
T
Buschow
Sonja I
SI
Ossendorp
Ferry A
FA
Melief
Cornelis J
CJ
Raposo
Graca
G
van Balkom
Bas W
BW
Stoorvogel
Willem
W
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology; D011992:Endosomes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D025801:Ubiquitin / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D025801:Ubiquitin