title: Immunoproteasome-specific inhibitors and their application.
abstract: Immunoproteasomes (IPs) containing the interferon-inducible subunits β1i (LMP2), β2i (MECL-1), and β5i (LMP7) alter proteasomal cleavage preference, optimise the generation of peptide ligands of MHC class I molecules, alter cytokine profile, influence T-helper cell differentiation, and play a role in T-cell survival. Small molecule inhibitors are useful tools for probing the role of the immunoproteasome in immune functions. Here, we describe different methods to characterise immunoproteasome-selective inhibitors. Thereby, we provide the methodology to analyse the specificity and cell permeability of immunoproteasome inhibitors, as well as to functionally investigate immunoproteasome inhibitors in antigen presentation.
authors.affiliation: Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany. michael.basler@uni-konstanz.de
authors.forename: Michael
authors.initials: M
authors.lastname: Basler
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D003546:Cysteine Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D047468:Immunoprecipitation / Q000379:methods; D007162:Immunoproteins / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D009842:Oligopeptides / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D061988:Proteasome Inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; D007162:Immunoproteins; D007376:Interleukin-2; D053759:Interleukin-23; D009842:Oligopeptides; C542291:PR-957; D061988:Proteasome Inhibitors; C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex