Title
Amyloid-like behavior of site-specifically citrullinated myelin oligodendrocyte protein (MOG) peptide fragments inside EBV infected B-cells influences their cytotoxicity and autoimmunogenicity.
Author
Can Araman, Miriam van Gent, Nico Meeuwenoord, Nicole Heijmans, Mikkel H. S. Marqvorsen, Bart W. Faber, Bert A. 't Hart, Sander I. van Kasteren
Year
2018
Journal
Biochemistry
Abstract
Multiple Sclerosis (MS) is an autoimmune disorder manifested via chronic inflammation, demyelination and neurodegeneration inside the central nervous system (CNS). 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 EBV-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 towards 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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Aggregation, Biochemistry