Journal article
Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection
H Liu, R Jain, J Guan, V Vuong, S Ishido, NL La Gruta, DH Gray, JA Villadangos, JD Mintern
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2016
DOI: 10.1084/jem.20160312
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..
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Grants
Awarded by Human Frontier Science Program
Funding Acknowledgements
This research was supported by National Health and Medical Research Council (NHMRC) of Australia program grants (1016629 and 1071916), NHMRC project grants (1078763, 1049724, and 1058193), a Human Frontier Science Program grant (RGP0064), and an Australian Research Council Discovery Project grant (DP110101383). H. Liu and J. Guan were supported by University of Melbourne International Research scholarships. N.L. La Gruta is a Sylvia and Charles Viertel Senior Medical Research Fellow, D.H. Gray is an NHMRC Career Development Fellow (Level 2, 1090236), and J.A. Villadangos is an NHMRC Principal Research Fellow (1058193). This work was made possible through Victorian State Government Operational Infrastructure support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.