![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| 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: |
Burster, T., Beck, A., Tolosa, E., Marin-Esteban, V., Rötzschke, O.  ORCID: https://orcid.org/0000-0001-8336-5248, 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: | https://doi.org/10.4049/jimmunol.172.9.5495 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
