Document Detail


Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells.
MedLine Citation:
PMID:  21059907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March-I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I-deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II-specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitin-dependent degradation of internalized pMHC-II.
Authors:
Even Walseng; Kazuyuki Furuta; Berta Bosch; Karis A Weih; Yohei Matsuki; Oddmund Bakke; Satoshi Ishido; Paul A Roche
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2010-11-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-20     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20465-70     Citation Subset:  IM    
Affiliation:
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal
Dendritic Cells / cytology,  immunology*,  metabolism*
Gene Expression Regulation / immunology*
Histocompatibility Antigens Class II / metabolism*
Immunoblotting
Immunoprecipitation
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence
Transfection
Ubiquitin-Protein Ligases / genetics,  metabolism*
Ubiquitination
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Histocompatibility Antigens Class II; EC 6.3.2.19/MARCH-I protein, mouse; EC 6.3.2.19/Ubiquitin-Protein Ligases
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