Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection

Haiyin Liu, Reema Jain, Jing Guan, Vivian Vuong, Satoshi Ishido, Nicole L. La Gruta, Daniel H. Gray, Jose A. Villadangos, Justine D. Mintern

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Major histocompatibility complex class II (MHC II) expression is tightly regulated, being subjected to cell type-specific mechanisms that closely control its levels at the cell surface. Ubiquitination by the E3 ubiquitin ligase MAR CH 1 regulates MHC II expression in dendritic cells and B cells. In this study, we demonstrate that the related ligase MAR CH 8 is responsible for regulating surface MHC II in thymic epithelial cells (TECs). March8-/- mice have elevated MHC II at the surface of cortical TECs and autoimmune regulator (AIRE)- medullary TECs (mTECs), but not AIRE+ mTECs. Despite this, thymic and splenic CD4+ T cell numbers and repertoires remained unaltered in March8-/- mice. Notably, the ubiquitination of MHC II by MAR CH 8 is controlled by CD83. Mice expressing a mutated form of CD83 (Cd83anu/anu mice) have impaired CD4+ T cell selection, but deleting March8 in Cd83anu/anu mice restored CD4+ T cell selection to normal levels. Therefore, orchestrated regulation of MHC II surface expression in TECs by MAR CH 8 and CD83 plays a major role in CD4+ T cell selection. Our results also highlight the specialized use of ubiquitinating machinery in distinct antigen-presenting cell types, with important functional consequences and implications for therapeutic manipulation.

Original languageEnglish
Pages (from-to)1695-1703
Number of pages9
JournalJournal of Experimental Medicine
Volume213
Issue number9
DOIs
Publication statusPublished - 8 Aug 2016

Cite this

Liu, Haiyin ; Jain, Reema ; Guan, Jing ; Vuong, Vivian ; Ishido, Satoshi ; La Gruta, Nicole L. ; Gray, Daniel H. ; Villadangos, Jose A. ; Mintern, Justine D. / Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 9. pp. 1695-1703.
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abstract = "Major histocompatibility complex class II (MHC II) expression is tightly regulated, being subjected to cell type-specific mechanisms that closely control its levels at the cell surface. Ubiquitination by the E3 ubiquitin ligase MAR CH 1 regulates MHC II expression in dendritic cells and B cells. In this study, we demonstrate that the related ligase MAR CH 8 is responsible for regulating surface MHC II in thymic epithelial cells (TECs). March8-/- mice have elevated MHC II at the surface of cortical TECs and autoimmune regulator (AIRE)- medullary TECs (mTECs), but not AIRE+ mTECs. Despite this, thymic and splenic CD4+ T cell numbers and repertoires remained unaltered in March8-/- mice. Notably, the ubiquitination of MHC II by MAR CH 8 is controlled by CD83. Mice expressing a mutated form of CD83 (Cd83anu/anu mice) have impaired CD4+ T cell selection, but deleting March8 in Cd83anu/anu mice restored CD4+ T cell selection to normal levels. Therefore, orchestrated regulation of MHC II surface expression in TECs by MAR CH 8 and CD83 plays a major role in CD4+ T cell selection. Our results also highlight the specialized use of ubiquitinating machinery in distinct antigen-presenting cell types, with important functional consequences and implications for therapeutic manipulation.",
author = "Haiyin Liu and Reema Jain and Jing Guan and Vivian Vuong and Satoshi Ishido and {La Gruta}, {Nicole L.} and Gray, {Daniel H.} and Villadangos, {Jose A.} and Mintern, {Justine D.}",
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Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection. / Liu, Haiyin; Jain, Reema; Guan, Jing; Vuong, Vivian; Ishido, Satoshi; La Gruta, Nicole L.; Gray, Daniel H.; Villadangos, Jose A.; Mintern, Justine D.

In: Journal of Experimental Medicine, Vol. 213, No. 9, 08.08.2016, p. 1695-1703.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection

AU - Liu, Haiyin

AU - Jain, Reema

AU - Guan, Jing

AU - Vuong, Vivian

AU - Ishido, Satoshi

AU - La Gruta, Nicole L.

AU - Gray, Daniel H.

AU - Villadangos, Jose A.

AU - Mintern, Justine D.

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