Epitope spreading and molecular mimicry as triggers of autoimmunity in the Theiler's virus-induced demyelinating disease model of multiple sclerosis.
The pathogenesis of multiple sclerosis (MS), a human demyelinating disease of the central nervous system (CNS), is currently unknown. It is widely thought that MS is an autoimmune disease which is supported by animal studies showing that myelin-specific CD4+ T cells can induce similar clinical disease in mice as observed in MS. However, the mechanism(s) of activation of these autoreactive CD4+ T cells are unknown. Although genetic susceptibility is important, other factors may be involved. Viral infections have long thought to be involved in the pathogenesis of MS although there exists little or no direct evidence implicating a role for a specific virus in MS pathogenesis. This review will discuss two models of virus-induced CNS autoimmunity, molecular mimicry and epitope spreading. These two mechanisms of activation of autoreactive T cells are presented in the context of MS.
Croxford
J Ludovic
JL
Department of Microbiology--Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, 60611, Chicago, IL, USA.
Olson
Julie K
JK
Miller
Stephen D
SD
D000818:Animals; D000956:Antigens, Viral; D015551:Autoimmunity; D018188:Cardiovirus Infections / Q000209:etiology / Q000276:immunology*; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology; D017945:Theilovirus / Q000472:pathogenicity*
D000956:Antigens, Viral; D000939:Epitopes