UBL3 Participates in the Early Stages of CD83-Dependent CD4 T Cell Selection

Abstract

CD83 is critical for CD4+ T cell selection. It regulates MHC II ubiquitination and turnover at the surface of thymic epithelial cells (TECs). The role of UBL3, a recently identified adaptor molecule for MHC II ubiquitination, is unknown in thymic selection. Here we demonstrate that UBL3 regulates MHC II in TECs and participates in CD4+ T cell selection. Deleting UBL3 in CD83 loss-of-function mice (Cd83anu/anu Ubl3−/−) increases MHC II on the surface of Cd83anu/anu TECs. This increase in surface MHC II correlates with increased positive selection of CD4+ T cells. Analysis of Cd83anu/anu and Cd83anu/anu Ubl3−/− mice identifies the CD4+ CD8low CD69+ stage of positive selection as the origin of ..