The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burster, T.
Right arrow Articles by Driessen, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burster, T.
Right arrow Articles by Driessen, C.
The Journal of Immunology, 2004, 172: 5495-5503.
Copyright © 2004 by The American Association of Immunologists

Cathepsin G, and Not the Asparagine-Specific Endoprotease, Controls the Processing of Myelin Basic Protein in Lysosomes from Human B Lymphocytes1

Timo Burster*, Alexander Beck{ddagger}, Eva Tolosa{dagger}, Viviana Marin-Esteban||, Olaf Rötzschke||, Kirsten Falk||, Alfred Lautwein*, Michael Reich*, Jens Brandenburg§, Gerold Schwarz§, Heinz Wiendl{dagger}, Arthur Melms{dagger}, Rainer Lehmann{ddagger}, Stefan Stevanovic, Hubert Kalbacher§ and Christoph Driessen2,*

Departments of * Medicine II, {dagger} Neurology, and {ddagger} Medicine IV, § Medical and Natural Sciences Research Centre, and Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany; and || Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

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.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
C. M. Costantino, H. L. Ploegh, and D. A. Hafler
Cathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells
J. Immunol., July 15, 2009; 183(2): 945 - 952.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. M. Costantino, H. C. Hang, S. C. Kent, D. A. Hafler, and H. L. Ploegh
Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation
J. Immunol., March 1, 2008; 180(5): 2876 - 2885.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
T. Burster, T. Giffon, M. E. Dahl, P. Bjorck, M. Bogyo, E. Weber, K. Mahmood, D. B. Lewis, and E. D. Mellins
Influenza A virus elevates active cathepsin B in primary murine DC
Int. Immunol., May 1, 2007; 19(5): 645 - 655.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Reich, P. F. van Swieten, V. Sommandas, M. Kraus, R. Fischer, E. Weber, H. Kalbacher, H. S. Overkleeft, and C. Driessen
Endocytosis targets exogenous material selectively to cathepsin S in live human dendritic cells, while cell-penetrating peptides mediate nonselective transport to cysteine cathepsins
J. Leukoc. Biol., April 1, 2007; 81(4): 990 - 1001.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Burster, A. Beck, E. Tolosa, P. Schnorrer, R. Weissert, M. Reich, M. Kraus, H. Kalbacher, H.-U. Haring, E. Weber, et al.
Differential Processing of Autoantigens in Lysosomes from Human Monocyte-Derived and Peripheral Blood Dendritic Cells
J. Immunol., November 1, 2005; 175(9): 5940 - 5949.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Maehr, H. C. Hang, J. D. Mintern, Y.-M. Kim, A. Cuvillier, M. Nishimura, K. Yamada, K. Shirahama-Noda, I. Hara-Nishimura, and H. L. Ploegh
Asparagine Endopeptidase Is Not Essential for Class II MHC Antigen Presentation but Is Required for Processing of Cathepsin L in Mice
J. Immunol., June 1, 2005; 174(11): 7066 - 7074.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Dengjel, O. Schoor, R. Fischer, M. Reich, M. Kraus, M. Muller, K. Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, et al.
From the Cover: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins
PNAS, May 31, 2005; 102(22): 7922 - 7927.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
F. C. Kurschus, R. Bruno, E. Fellows, C. S. Falk, and D. E. Jenne
Membrane receptors are not required to deliver granzyme B during killer cell attack
Blood, March 1, 2005; 105(5): 2049 - 2058.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.