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MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway
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MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway
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Journal Article
MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway
2018
Overview
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
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antigen Presentation - physiology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CRISPR
/ Dendritic Cells - immunology
/ Gene Expression Regulation - immunology
/ Histocompatibility Antigens Class I - genetics
/ Histocompatibility Antigens Class I - immunology
/ Histocompatibility Antigens Class II - genetics
/ Histocompatibility Antigens Class II - immunology
/ Major histocompatibility complex
/ Medicine and Health Sciences
/ Mice
/ Proteins
/ Research and Analysis Methods
/ Ubiquitin-Protein Ligases - genetics
