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

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

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5495-503
Number of pages9
JournalJournal of Immunology
Issue number9
Publication statusPublished - May 1 2004
Externally publishedYes


  • 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
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't


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