Post-translational modification of central nervous system proteins, including glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP), through citrullination of arginine residues, may lead to exposure of neoepitopes, triggering autoimmunity.
Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG).
Through its enzymatic activity PAD2 converts myelin basic protein (MBP) arginines into citrullines - an event that may favour autoimmunity - while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling.
Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice.
Here we found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance was broken and autoimmunity was induced by infection with a virus that did not express MBP cross-reactive epitopes and did not depend on bystander activation.
The temporal characteristics of the MBP-specific T-cell repertoire described here are relevant to therapeutic strategies targeting autoantigen-specific T cells in multiple sclerosis and other autoimmune diseases.
MBP TCR transgenic models are playing an important role in defining mechanisms by which infectious agents trigger autoimmune disease as well as defining mechanisms by which tolerance is induced to distinct epitopes within self-antigens.
Autoimmunity may also play a role; antibodies against myelin basic protein are often found in children with autism, who also have increased eosinophil and basophil response to IgE-mediated reactions.