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 language | English |
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Pages (from-to) | 2994-9 |
Number of pages | 6 |
Journal | Molecular Immunology |
Volume | 46 |
Issue number | 15 |
DOIs | |
Publication status | Published - 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