MHC II In dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways

Buschow, Sonja I., Nolte-'t Hoen, Esther N. M., van Niel, Guillaume, Pols, Maaike S., ten Broeke, Toine, Lauwen, Marjolein, Ossendorp, Ferry, Melief, Cornelis J. M., Raposo, Graca, Wubbolts, Richard, Wauben, Marca H. M. and Stoorvogel, Willem (2009) MHC II In dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic, 10 10: 1528-1542. doi:10.1111/j.1600-0854.2009.00963.x


Author Buschow, Sonja I.
Nolte-'t Hoen, Esther N. M.
van Niel, Guillaume
Pols, Maaike S.
ten Broeke, Toine
Lauwen, Marjolein
Ossendorp, Ferry
Melief, Cornelis J. M.
Raposo, Graca
Wubbolts, Richard
Wauben, Marca H. M.
Stoorvogel, Willem
Title MHC II In dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
1600-0854
Publication date 2009-10
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2009.00963.x
Volume 10
Issue 10
Start page 1528
End page 1542
Total pages 15
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract 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.
Keyword Dendritic cells
Exosome
MHC class II
Multivesicular body
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Wed, 25 Jul 2012, 11:08:38 EST by Susan Allen on behalf of Institute for Molecular Bioscience