MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway

PloS One
Kayla R WilsonJustine D Mintern

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.

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Citations

Aug 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Haiyin LiuJustine D Mintern
Aug 16, 2019·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·Thaise Pinto de MeloRoberto Carvalheiro
Oct 22, 2020·Cell Biology International·Nuan WangChengxia Liu
Dec 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hei Jung KimPaul A Roche

Related Concepts

MARCH1 protein, mouse
Metazoa
Immune-Associated Antigens
B-Lymphocytes
Veiled Cells
Human Class I Antigens
Gene Deletion
Antigen Processing
Mice, Knockout
Suppressor T-Lymphocytes, CD8-Positive

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