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

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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., Beck, A., Tolosa, E., Marin-Esteban, V., Roetzschke, O., Falk, K., Lautwein, A., Reich, M., Brandenburg, J., Schwarz, G., Wiendl, H., Melms, A., Lehmann, R., Stevanovic, S., 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
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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