Pharmacodynamic Monitoring of RO5459072, a Small Molecule Inhibitor of Cathepsin S.

ABSTRACT: Major histocompatibility complex class II (MHCII)-restricted antigen priming of CD4⁺ T cells is both involved in adaptive immune responses and the pathogenesis of autoimmune diseases. Degradation of invariant chain Ii, a protein that prevents premature peptide loading, is a prerequisite for nascent MHCII-peptide complex formation. A key proteolytic step in this process is mediated by cathepsin S. Inhibition of this cysteine protease is known to result in the intracellular accumulation of Lip10 in B cells. Here, we describe the development and application of a neoepitope-based flow cytometry assay measuring accumulation of Lip10. This novel method enabled the investigation of cathepsin S-dependent MHCII maturation in professional antigen-presenting cell (APC) subsets. Inhibition

SUBMITTER: Theron M 

PROVIDER: S-EPMC5512459 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature