Amyloid-like Behavior of Site-Specifically Citrullinated Myelin Oligodendrocyte Protein (MOG) Peptide Fragments inside EBV-Infected B-Cells Influences Their Cytotoxicity and Autoimmunogenicity
| Autor: | Can Araman, Mikkel H. S. Marqvorsen, Nico J. Meeuwenoord, Bert A. 't Hart, Bart W. Faber, Sander I. van Kasteren, Ward Doelman, Miriam E. van Gent, Nicole Heijmans |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Amyloid
Herpesvirus 4 Human T-Lymphocytes Amyloidogenic Proteins Biochemistry Protein Aggregation Pathological Article Myelin oligodendrocyte glycoprotein Cell Line 03 medical and health sciences Myelin medicine Animals Humans Amino Acid Sequence Benzothiazoles Peptide sequence 0303 health sciences B-Lymphocytes biology Chemistry Multiple sclerosis 030302 biochemistry & molecular biology Neurodegeneration Citrullination Callithrix Dendritic Cells Multiple Sclerosis Chronic Progressive medicine.disease Oligodendrocyte Peptide Fragments Recombinant Proteins Mice Inbred C57BL medicine.anatomical_structure Immunology biology.protein Myelin-Oligodendrocyte Glycoprotein |
| Zdroj: | Biochemistry Biochemistry, 58(6), 763-775 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Multiple sclerosis (MS) is an autoimmune disorder manifested via chronic inflammation, demyelination, and neurodegeneration inside the central nervous system. The progressive phase of MS is characterized by neurodegeneration, but unlike classical neurodegenerative diseases, amyloid-like aggregation of self-proteins has not been documented. There is evidence that citrullination protects an immunodominant peptide of human myelin oligodendrocyte glycoprotein (MOG34–56) against destructive processing in Epstein-Barr virus-infected B-lymphocytes (EBV-BLCs) in marmosets and causes exacerbation of ongoing MS-like encephalopathies in mice. Here we collected evidence that citrullination of MOG can also lead to amyloid-like behavior shifting the disease pathogenesis toward neurodegeneration. We observed that an immunodominant MOG peptide, MOG35–55, displays amyloid-like behavior upon site-specific citrullination at positions 41, 46, and/or 52. These amyloid aggregates are shown to be toxic to the EBV-BLCs and to dendritic cells at concentrations favored for antigen presentation, suggesting a role of amyloid-like aggregation in the pathogenesis of progressive MS. |
| Databáze: | OpenAIRE |
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