WEHI Special Ubiquitin Signalling Seminar hosted by Bekky Feltham & Grant Dewson
 

Professor Justine Mintern

Department of Biochemistry and Pharmacology, University of Melbourne, Bio21 Institute

Unexpected roles for ubiquitin in immunity

Davis Auditorium

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Including Q&A session

Expression of immune receptors at the cell surface is a key determinant of immunity. Here, we have aimed to analyse the role of ubiquitination in immune receptor trafficking. Ubiquitination regulates the cell surface display of MHC II (major antigen presenting molecule) and CD86 (co-stimulatory molecule). First, we have identified the ubiquitin codes (ubiquitin chain linkage types) associated with MHC II in primary murine immune cells. Second, we have identified a new role for MHC II ubiquitination in the regulation of dendritic cell homeostasis that involves a surprising intersection between innate and adaptive immunity. Third, we have performed a genome-wide CRISPR/Cas9 screen to identify molecular participants in ubiquitin-mediated immune trafficking. We identified ubiquitin like 3 (Ubl3), a previously uncharacterised mammalian protein, as a novel regulator of MHC II and CD86 trafficking. We describe new roles for Ubl3 in dendritic cells, B cells and thymic epithelium using Ubl3-deficient mice. Finally, we have conducted boutique CRISPR/Cas9 screens to identify new E3 Ub ligases that regulate an array of immune receptors at the surface of dendritic cells. In summary, our analysis provides significant advances to understanding how immune receptors are trafficked inside cells with important consequences for immunity.  

All welcome!