Immunoproteasome-specific inhibitors and their application

Methods Mol Biol. 2012;832:391-401. doi: 10.1007/978-1-61779-474-2_27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine Endopeptidases / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Histocompatibility Antigens Class I / immunology
  • Immunoprecipitation / methods
  • Immunoproteins / antagonists & inhibitors*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-23 / biosynthesis
  • Oligopeptides / pharmacology*
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Enzyme Inhibitors
  • Histocompatibility Antigens Class I
  • Immunoproteins
  • Interleukin-2
  • Interleukin-23
  • Oligopeptides
  • PR-957
  • Proteasome Inhibitors
  • LMP-2 protein
  • Interferon-gamma
  • Cysteine Endopeptidases
  • LMP7 protein
  • PSMB10 protein, human
  • Proteasome Endopeptidase Complex