Application of specific cell permeable cathepsin G inhibitors resulted in reduced antigen processing in primary dendritic cells

Michael Reich, Adam Lesner, Anna Legowska, Marcin Sieńczyk, Jozef Oleksyszyn, Bernhard O Boehm, Timo Burster

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The serine protease cathepsin G (CatG) is expressed in primary antigen-presenting cells and regulates autoantigen processing in CatG pre-loaded fibroblasts. To further investigate the function of CatG in the major histocompatibility complex (MHC) class II loading compartments, a specific, cell permeable CatG-inhibitor is needed. In this study, several CatG-inhibitors were tested for their ability to penetrate the cell membrane of peripheral blood mononuclear cells (PBMC). We find that the commercially available reversible CatG-specific inhibitor I (CatG inhibitor) and the irreversible Suc-Val-Pro-Phe(P) (OPh)(2) (Suc-VPF) are both cell permeable and specifically inhibit intracellular CatG in the PBMC. Furthermore, selective inhibition of CatG resulted in reduced tetanus toxin C-fragment (TTC) and hemagglutinin (HA) processing and presentation to CD4(+) T cells. We conclude that these CatG inhibitors can be used for both antigen-processing studies and for modulation of T cell response in situ and in vivo.

Original languageEnglish
Pages (from-to)2994-9
Number of pages6
JournalMolecular Immunology
Volume46
Issue number15
DOIs
Publication statusPublished - Sep 2009

Keywords

  • Antigen Presentation
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Cathepsin G
  • Cathepsins
  • Cell Membrane Permeability
  • Dendritic Cells
  • Hemagglutinins
  • Humans
  • Peptide Fragments
  • Serine Endopeptidases
  • Serine Proteinase Inhibitors
  • Tetanus Toxin
  • Journal Article
  • Research Support, Non-U.S. Gov't

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