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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

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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. / Burster, Timo; Beck, Alexander; Tolosa, Eva; Marin-Esteban, Viviana; Rötzschke, Olaf; Falk, Kirsten; Lautwein, Alfred; Reich, Michael; Brandenburg, Jens; Schwarz, Gerold; Wiendl, Heinz; Melms, Arthur; Lehmann, Rainer; Stevanovic, Stefan; Kalbacher, Hubert; Driessen, Christoph.

In: J IMMUNOL, Vol. 172, No. 9, 01.05.2004, p. 5495-503.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Burster, T, Beck, A, Tolosa, E, Marin-Esteban, V, Rötzschke, O, Falk, K, Lautwein, A, Reich, M, Brandenburg, J, Schwarz, G, Wiendl, H, Melms, A, Lehmann, R, Stevanovic, S, Kalbacher, H & Driessen, C 2004, 'Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes', J IMMUNOL, vol. 172, no. 9, pp. 5495-503.

APA

Burster, T., Beck, A., Tolosa, E., Marin-Esteban, V., Rötzschke, O., Falk, K., Lautwein, A., Reich, M., Brandenburg, J., Schwarz, G., Wiendl, H., Melms, A., Lehmann, R., Stevanovic, S., Kalbacher, H., & Driessen, C. (2004). Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes. J IMMUNOL, 172(9), 5495-503.

Vancouver

Burster T, Beck A, Tolosa E, Marin-Esteban V, Rötzschke O, Falk K et al. Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes. J IMMUNOL. 2004 May 1;172(9):5495-503.

Bibtex

@article{64f6831f6e8b42cb86e1078d57b65d9e,
title = "Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes",
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 = "Adult, Amino Acid Sequence, Animals, Antigen-Presenting Cells, Asparagine, B-Lymphocyte Subsets, Cathepsin G, Cathepsins, Cell Line, Cell Line, Transformed, Cell Separation, Cysteine Endopeptidases, Humans, Hydrolysis, Lymphocyte Activation, Lysine, Lysosomes, Mice, Molecular Sequence Data, Myelin Basic Protein, Phenylalanine, Protein Processing, Post-Translational, Serine, Serine Endopeptidases",
author = "Timo Burster and Alexander Beck and Eva Tolosa and Viviana Marin-Esteban and Olaf R{\"o}tzschke and Kirsten Falk and Alfred Lautwein and Michael Reich and Jens Brandenburg and Gerold Schwarz and Heinz Wiendl and Arthur Melms and Rainer Lehmann and Stefan Stevanovic and Hubert Kalbacher and Christoph Driessen",
year = "2004",
month = may,
day = "1",
language = "English",
volume = "172",
pages = "5495--503",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

RIS

TY - JOUR

T1 - Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes

AU - Burster, Timo

AU - Beck, Alexander

AU - Tolosa, Eva

AU - Marin-Esteban, Viviana

AU - Rötzschke, Olaf

AU - Falk, Kirsten

AU - Lautwein, Alfred

AU - Reich, Michael

AU - Brandenburg, Jens

AU - Schwarz, Gerold

AU - Wiendl, Heinz

AU - Melms, Arthur

AU - Lehmann, Rainer

AU - Stevanovic, Stefan

AU - Kalbacher, Hubert

AU - Driessen, Christoph

PY - 2004/5/1

Y1 - 2004/5/1

N2 - 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.

AB - 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.

KW - Adult

KW - Amino Acid Sequence

KW - Animals

KW - Antigen-Presenting Cells

KW - Asparagine

KW - B-Lymphocyte Subsets

KW - Cathepsin G

KW - Cathepsins

KW - Cell Line

KW - Cell Line, Transformed

KW - Cell Separation

KW - Cysteine Endopeptidases

KW - Humans

KW - Hydrolysis

KW - Lymphocyte Activation

KW - Lysine

KW - Lysosomes

KW - Mice

KW - Molecular Sequence Data

KW - Myelin Basic Protein

KW - Phenylalanine

KW - Protein Processing, Post-Translational

KW - Serine

KW - Serine Endopeptidases

M3 - SCORING: Journal article

C2 - 15100291

VL - 172

SP - 5495

EP - 5503

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 9

ER -