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

Abstract

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

References

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Citations

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
Lysosomes
Polypeptides
Endosomes
Immunoblotting, Reverse
Biotinylation
Short Hairpin RNA
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