PMID- 17174123 OWN - NLM STAT- MEDLINE DCOM- 20070207 LR - 20061218 IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 25 IP - 6 DP - 2006 Dec TI - Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination. PG - 885-94 AB - 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. FAU - van Niel, Guillaume AU - van Niel G AD - Faculty of Veterinary Medicine, Department of Biochemistry & Cell Biology, Utrecht University, P.O. Box 80.176, NL-3508 TD, Utrecht, The Netherlands. FAU - Wubbolts, Richard AU - Wubbolts R FAU - Ten Broeke, Toine AU - Ten Broeke T FAU - Buschow, Sonja I AU - Buschow SI FAU - Ossendorp, Ferry A AU - Ossendorp FA FAU - Melief, Cornelis J AU - Melief CJ FAU - Raposo, Graca AU - Raposo G FAU - van Balkom, Bas W AU - van Balkom BW FAU - Stoorvogel, Willem AU - Stoorvogel W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Ubiquitin) SB - IM CIN - Immunity. 2006 Dec;25(6):857-9. PMID: 17174926 MH - Animals MH - Antigen Presentation/*immunology MH - Cell Differentiation MH - Cell Line MH - Cell Membrane/immunology/*metabolism MH - Dendritic Cells/cytology/immunology/*metabolism MH - Endocytosis/immunology MH - Endosomes/metabolism MH - Histocompatibility Antigens Class II/immunology/*metabolism MH - Immunoprecipitation MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Confocal MH - Microscopy, Immunoelectron MH - Ubiquitin/*metabolism EDAT- 2006/12/19 09:00 MHDA- 2007/02/08 09:00 CRDT- 2006/12/19 09:00 PHST- 2006/10/12 00:00 [received] PHST- 2006/11/13 00:00 [accepted] PHST- 2006/12/19 09:00 [pubmed] PHST- 2007/02/08 09:00 [medline] PHST- 2006/12/19 09:00 [entrez] AID - S1074-7613(06)00516-4 [pii] AID - 10.1016/j.immuni.2006.11.001 [doi] PST - ppublish SO - Immunity. 2006 Dec;25(6):885-94. doi: 10.1016/j.immuni.2006.11.001.