Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
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N. Katunuma
Abstract
Eleven human cathepsins have been identified, however, the in vivo roles of individual cathepsins are still largely unknown. In this brief review we will summarize the functions of individual cathepsins in antigen processing and presentation, which are the initial steps of the immune response. Two general inhibitors of papainlike cysteine proteases, E-64 and pyridoxal phosphate, can completely suppress antigen presentation in vivo. To evaluate the contribution of individual cathepsins, specific inhibitors have been developed based on cathepsin tertiary structures: CA-074 for cathepsin B, CLIK-148 and -195 for cathepsin L, CLIK-60 for cathepsin S. Administration of CA-074, a cathepsin B inhibitor, suppresses the response to exogenous antigens, such as hepatitis B virus antigen, ovalbumin and Leishmania major antigen, and induces switching of the helper T cell responses from Th-2 to Th-1 of CD4+ T cells, thereby downregulating the production of IgE and IgG1. Administration of the cathepsin S inhibitor CLIK-60 impairs presentation of an autoantigen, α-fodrin, in Sjogrens syndrome and suppresses the Th-1 response and autoantibody production.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Vito Turk – 30 Years of Research on Cysteine Proteases and Their Inhibitors
- Family C1 Cysteine Proteases: Biological Diversity or Redundancy?
- Molecular Regulation of Human Cathepsin B: Implication in Pathologies
- Caspases and Neuronal Development
- Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
- Managing Peptidases in the Genomic Era
- Insights into the Roles of Cathepsins in Antigen Processing and Presentation Revealed by Specific Inhibitors
- Cleavage Site Specificity of Cathepsin K toward Cartilage Proteoglycans and Protease Complex Formation
- Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases
- Isolation and Characterization of a Novel and Potent Inhibitor of Arg-Gingipain from Streptomyces sp. Strain FA-70
- Procongopain from Trypanosoma congolense Is Processed at Basic pH: An Unusual Feature among Cathepsin L-Like Cysteine Proteases
- Attenuated Kinin Release from Human Neutrophil Elastase-Pretreated Kininogens by Tissue and Plasma Kallikreins
- Effect of Plant Kunitz Inhibitors from Bauhinia bauhinioides and Bauhinia rufa on Pulmonary Edema Caused by Activated Neutrophils
- Revisiting Ubiquity and Tissue Specificity of Human Calpains
- The Calpastatin-Derived Calpain Inhibitor CP1B Reduces mRNA Expression of Matrix Metalloproteinase-2 and -9 and Invasion by Leukemic THP-1 Cells
- Heat Stress-Dependent DNA Binding of Arabidopsis Heat Shock Transcription Factor HSF1 to Heat Shock Gene Promoters in Arabidopsis Suspension Culture Cells in vivo
- T47-D Cells and Type V Collagen: A Model for the Study of Apoptotic Gene Expression by Breast Cancer Cells
