Internalizing MHC class II-peptide complexes are ubiquitinated in early endosomes and targeted for lysosomal degradation

Proceedings of the National Academy of Sciences of the United States of America
Kazuyuki FurutaPaul A Roche


As sentinels of the immune system, dendritic cells (DCs) continuously generate and turnover antigenic peptide-MHC class II complexes (pMHC-II). pMHC-II generation is a complex process that involves many well-characterized MHC-II biosynthetic intermediates; however, the mechanisms leading to MHC-II turnover/degradation are poorly understood. We now show that pMHC-II complexes undergoing clathrin-independent endocytosis from the DC surface are efficiently ubiquitinated by the E3 ubiquitin ligase March-I in early endosomes, whereas biosynthetically immature MHC-II-Invariant chain (Ii) complexes are not. The inability of MHC-II-Ii to serve as a March-I substrate is a consequence of Ii sorting motifs that divert the MHC-II-Ii complex away from March-I(+) early endosomes. When these sorting motifs are mutated, or when clathrin-mediated endocytosis is inhibited, MHC-II-Ii complexes internalize by using a clathrin-independent endocytosis pathway and are now ubiquitinated as efficiently as pMHC-II complexes. These data show that the selective ubiquitination of internalizing surface pMHC-II in March-I(+) early endosomes promotes degradation of "old" pMHC-II and spares forms of MHC-II that have not yet loaded antigenic peptides or have no...Continue Reading


Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Paul A RocheE O Long
Apr 1, 1998·Nature·J Banchereau, R M Steinman
Mar 18, 2005·Annual Review of Immunology·E Sergio Trombetta, Ira Mellman
May 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Peter J McCormickJuan S Bonifacino
Jan 11, 2007·Journal of Microscopy·S Bolte, F P Cordelières
Jan 27, 2007·The EMBO Journal·Yohei MatsukiSatoshi Ishido
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Aude de GassartEvelina Gatti
Apr 5, 2008·European Journal of Immunology·Jacques ThibodeauViktor Steimle
Jul 2, 2009·Traffic·Marie-Elaine GauvreauJacques Thibodeau
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Even WalsengPaul A Roche
Jul 16, 2011·Molecular Biology of the Cell·Craig A EysterJulie G Donaldson
Mar 13, 2012·Annual Review of Biochemistry·Jason A MacGurnScott D Emr
Jan 10, 2013·Annual Review of Immunology·Janice S BlumPeter Cresswell


Aug 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kyung-Jin ChoPaul A Roche
Mar 16, 2016·The Journal of Cell Biology·Danielle E JohnsonSergio Grinstein
Jun 19, 2015·Immunological Reviews·Jaehak Oh, Jeoung-Sook Shin
May 15, 2015·Journal of Immunological Methods·Cassandra M HenniesEdith M Janssen
Apr 19, 2015·Seminars in Immunology·Michael L van de WeijerEmmanuel J H J Wiertz
Jan 20, 2015·Current Opinion in Immunology·Sharad K Mittal, Paul A Roche
Feb 28, 2015·Nature Reviews. Immunology·Paul A Roche, Kazuyuki Furuta
Jan 21, 2015·The Journal of Cell Biology·Takanobu OtomoThomas Braulke
Jan 31, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyung-Jin ChoPaul A Roche
Jan 14, 2021·Signal Transduction and Targeted Therapy·Xiaofei Zhou, Shao-Cong Sun
Dec 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hei Jung KimPaul A Roche

Related Concepts

Veiled Cells
Ir Genes
HeLa Cells
Immunoblotting, Reverse
Short Hairpin RNA
Multiprotein Complexes

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

© 2021 Meta ULC. All rights reserved