Abstract

Three lines of inquiry will be presented. The first part of this talk will focus on the role of the serine protease, cathepsin G, in processing of antigens for presentation to CD4 T cells by MHC class II molecules. A novel affinity probe was used to demonstrate that cathepsin G enzymatic activity is elevated in antigen-presenting cells from patients with type 1 diabetes. This enzyme was shown to play a major role in the processing of proinsulin, an important diabetes autoantigen, into fragments recognised by patients’ CD4 T cells. In a second line of investigation, cathepsin G cleaved detergent-solubilised and recombinant soluble, but not membrane-bound MHC class II molecules, raising the possibility that this enzyme may initiate the disposal of class II molecules dislocated from the plasma membrane. Finally, Epstein-Barr virus was shown to evade immune recognition by CD4 + T cells in part by modulating the level of cathepsin D, an aspartyl protease.