| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Medicine II,
Neurology, and
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:
|
|
 |
|
  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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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 |
