Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells.


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.

DOI: 10.1073/pnas.1010990107


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@article{Walseng2010UbiquitinationRM, title={Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells.}, author={Even Walseng and Kazuyuki Furuta and Berta Bosch and Karis A. Weih and Yohei Matsuki and Oddmund Bakke and Satoshi Ishido and Paul Roche}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2010}, volume={107 47}, pages={20465-70} }