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Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes

Item Type:Article
Title:Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes
Creators Name:Burster, T. and Beck, A. and Tolosa, E. and Marin-Esteban, V. and Roetzschke, O. and Falk, K. and Lautwein, A. and Reich, M. and Brandenburg, J. and Schwarz, G. and Wiendl, H. and Melms, A. and Lehmann, R. and Stevanovic, S. and Kalbacher, H. and Driessen, C.
Abstract:The asparagine-specific endoprotease (AEP) controls lysosomal processing of the potential autoantigen myelin basic protein (MBP) by human B lymphoblastoid cells, a feature implicated in the immunopathogenesis of multiple sclerosis. In this study, we demonstrate that freshly isolated human B lymphocytes lack significant AEP activity and that cleavage by AEP is dispensable for proteolytic processing of MBP in this type of cell. Instead, cathepsin (Cat) G, a serine protease that is not endogenously synthesized by B lymphocytes, is internalized from the plasma membrane and present in lysosomes from human B cells where it represents a major functional constituent of the proteolytic machinery. CatG initialized and dominated the destruction of intact MBP by B cell-derived lysosomal extracts, degrading the immunodominant MBP epitope and eliminating both its binding to MHC class II and a MBP-specific T cell response. Degradation of intact MBP by CatG was not restricted to a lysosomal environment, but was also performed by soluble CatG. Thus, the abundant protease CatG might participate in eliminating the immunodominant determinant of MBP. Internalization of exogenous CatG represents a novel mechanism of professional APC to acquire functionally dominant proteolytic activity that complements the panel of endogenous lysosomal enzymes.
Keywords:Amino Acid Sequence, Antigen-Presenting Cells, Asparagine, B-Lymphocyte Subsets, Cathepsins, Cell Line, Cell Separation, Cysteine Endopeptidases, Hydrolysis, Lymphocyte Activation, Lysine, Lysosomes, Molecular Sequence Data, Myelin Basic Proteins, Phenylalanine, Post-Translational Protein Processing, Serine, Serine Endopeptidases, Transformed Cell Line, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:172
Number:9
Page Range:5495-5503
Date:1 January 2004
Official Publication:http://www.jimmunol.org/cgi/content/abstract/172/9/5495
PubMed:View item in PubMed

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