Functional role of epitope spreading in the chronic pathogenesis of autoimmune and virus-induced demyelinating diseases.
These results support a model of epitope spreading (Figure 4) wherein localized virus-specific T cell-mediated inflammatory processes lead to the recruitment/activation of CNS-resident APCs which can serve both as effector cells for myelin destruction and as APCs which efficiently process/present endogenous self epitopes to autoreactive T cells. Thus, inflammatory responses induced by viruses which trigger pro-inflammatory Th1 responses and have the ability to persist in genetically susceptible hosts, may lead to chronic organ-specific autoimmune disease via epitope spreading. Regardless of the specificity of the T cells (myelin peptides in R-EAE or TMEV epitopes in TMEV-IDD) responsible for initiating myelin destruction, epitope spreading plays an important contributory role in the chronic disease process in genetically susceptible SJL mice. Epitope spreading has obvious important implications to the design of antigen-specific therapies for the potential treatment of MS and other autoimmune diseases. This process indicates that autoimmune diseases are evolving pathologies and that the specificity of the effector autoantigen-specific T cells varies during the chronic disease process.
Miller
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Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611, USA.
Eagar
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TN
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology; D000939:Epitopes; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D017945:Theilovirus / Q000472:pathogenicity
D000939:Epitopes; C571326:MOG protein, human; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein