Specific cathepsin B inhibitor is cell-permeable and activates presentation of TTC in primary human dendritic cells

Michael Reich, Ewa Wieczerzak, Elzbieta Jankowska, David Palesch, Bernhard O Boehm, Timo Burster

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Cathepsins of the cysteine, aspartyl, and serine classes are involved in antigen processing in the class II major histocompatibility complex (MHC) loading compartment. Investigation of these proteases in living cells is difficult to perform due to the lack of highly specific cell-permeable inhibitors. Recently, a highly selective cathepsin B (CatB) inhibitor, Z-Arg-Leu-Arg-alpha-aza-glycyl-Ile-Val-OMe (ZRLR), was described. We found that ZRLR is cell-permeable and specifically inhibits CatB, in contrast to the CatB inhibitor, CA074-OMe, which blocks cysteine cathepsins in addition to CatB in primary human antigen-presenting cells (APC). Furthermore, we compared both CA074-OMe and ZRLR in the ability to alter tetanus toxin C-fragment (TTC) presentation to T cells by different APC. As a result, we found enhanced presentation of TTC in the presence of ZRLR, as determined by detection of pro-inflammatory cytokines. We conclude that ZRLR is a specific, cell-permeable CatB inhibitor which can be used for antigen presenting studies in situ.

Original languageEnglish
Pages (from-to)155-9
Number of pages5
JournalImmunology Letters
Volume123
Issue number2
DOIs
Publication statusPublished - Apr 27 2009

Keywords

  • Antigen Presentation
  • Cathepsin B
  • Cell Membrane Permeability
  • Cysteine Proteinase Inhibitors
  • Dendritic Cells
  • Dipeptides
  • Humans
  • Interferon-gamma
  • Interleukin-17
  • Oligopeptides
  • Peptide Fragments
  • T-Lymphocytes
  • Tetanus Toxin
  • Tumor Necrosis Factor-alpha
  • Journal Article

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