MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway
- Author(s)
- Wilson, KR; Liu, H; Healey, G; Vuong, V; Ishido, S; Herold, MJ; Villadangos, JA; Mintern, JD;
- Details
- Publication Year 2018,Volume 13,Issue #7,Page e0200540
- Journal Title
- PLoS One
- Publication Type
- Journal Article
- Abstract
- Major histocompatibility complex class II (MHC II) expression and turn-over are regulated via its ubiquitination by the membrane associated RING-CH 1 (MARCH1) E3 ligase. Unexpectedly, we show that MHC II ubiquitination also impacts MHC I. Lack of MARCH1 in B cells and dendritic cells (DCs) resulted in a significant reduction in surface MHC I expression. This decrease was not directly caused by changes in MARCH1 ubiquitination of MHC I but indirectly by altered MHC II trafficking in the absence of its ubiquitination. Deletion of MHC II in March1-/- cells restored normal MHC I surface expression and replacement of wild type MHC II by a variant that could not be ubiquitinated caused a reduction in MHC I expression. Furthermore, these cells displayed inefficient presentation of peptide and protein antigen via MHC I to CD8+ T cells. In summary, we describe an unexpected intersection between MHC I and MHC II such that the surface expression of both molecules are indirectly and directly regulated by MARCH1 ubiquitination, respectively.
- Publisher
- PLOS
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 30001419
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0200540
- Open Access at Publisher's Site
- https://doi.org/10.1371/journal.pone.0200540
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-07-23 09:32:18
Last Modified: 2018-07-23 10:36:33