PMID- 19682328 OWN - NLM STAT- MEDLINE DCOM- 20100305 LR - 20090918 IS - 1600-0854 (Electronic) IS - 1398-9219 (Linking) VI - 10 IP - 10 DP - 2009 Oct TI - MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. PG - 1528-42 LID - 10.1111/j.1600-0854.2009.00963.x [doi] AB - Dendritic cells (DCs) express major histocompatibility complex class II (MHC II) to present peptide antigens to T cells. In immature DCs, which bear low cell surface levels of MHC II, peptide-loaded MHC II is ubiquitinated. Ubiquitination drives the endocytosis and sorting of MHC II to the luminal vesicles of multivesicular bodies (MVBs) for lysosomal degradation. Ubiquitination of MHC II is abrogated in activated DCs, resulting in an increased cell surface expression. We here provide evidence for an alternative MVB sorting mechanism for MHC II in antigen-loaded DCs, which is triggered by cognately interacting antigen-specific CD4+ T cells. At these conditions, DCs generate MVBs with MHC II and CD9 carrying luminal vesicles that are secreted as exosomes and transferred to the interacting T cells. Sorting of MHC II into exosomes was, in contrast to lysosomal targeting, independent of MHC II ubiquitination but rather correlated with its incorporation into CD9 containing detergent-resistant membranes. Together, these data indicate two distinct MVB pathways: one for lysosomal targeting and the other for exosome secretion. FAU - Buschow, Sonja I AU - Buschow SI AD - Faculty of Veterinary Medicine, Department of Biochemistry & Cell Biology, Utrecht University, The Netherlands. FAU - Nolte-'t Hoen, Esther N M AU - Nolte-'t Hoen EN FAU - van Niel, Guillaume AU - van Niel G FAU - Pols, Maaike S AU - Pols MS FAU - ten Broeke, Toine AU - ten Broeke T FAU - Lauwen, Marjolein AU - Lauwen M FAU - Ossendorp, Ferry AU - Ossendorp F FAU - Melief, Cornelis J M AU - Melief CJ FAU - Raposo, Graca AU - Raposo G FAU - Wubbolts, Richard AU - Wubbolts R FAU - Wauben, Marca H M AU - Wauben MH FAU - Stoorvogel, Willem AU - Stoorvogel W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090714 PL - England TA - Traffic JT - Traffic (Copenhagen, Denmark) JID - 100939340 RN - 0 (Histocompatibility Antigens Class II) SB - IM MH - Animals MH - Blotting, Western MH - CD4-Positive T-Lymphocytes/immunology/*metabolism/ultrastructure MH - Cell Membrane/metabolism/ultrastructure MH - Coculture Techniques MH - Dendritic Cells/immunology/*metabolism/ultrastructure MH - Electrophoresis, Polyacrylamide Gel MH - Exosomes/immunology/*metabolism/ultrastructure MH - Histocompatibility Antigens Class II/genetics/*metabolism MH - Immunoprecipitation MH - Lysosomes/immunology/*metabolism/ultrastructure MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Fluorescence MH - Microscopy, Immunoelectron MH - Multivesicular Bodies/immunology/*metabolism/ultrastructure MH - Protein Transport MH - Spleen/cytology MH - Ubiquitination EDAT- 2009/08/18 09:00 MHDA- 2010/03/06 06:00 CRDT- 2009/08/18 09:00 PHST- 2009/08/18 09:00 [entrez] PHST- 2009/08/18 09:00 [pubmed] PHST- 2010/03/06 06:00 [medline] AID - TRA963 [pii] AID - 10.1111/j.1600-0854.2009.00963.x [doi] PST - ppublish SO - Traffic. 2009 Oct;10(10):1528-42. doi: 10.1111/j.1600-0854.2009.00963.x. Epub 2009 Jul 14.