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Functional Role of Epitope Spreading in the Chronic Pathogenesis of Autoimmune and Virus-Induced Demyelinating Diseases

  • Stephen D. Miller
  • Todd N. Eagar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 490)

Abstract

Precise delineation of the mechanisms involved in the initiation and progression of autoimmune diseases is one of the most enigmatic issues in the field of immunology. It is clear that the etiology of many autoimmune diseases is influenced by both genetic and environmental factors. This is certainly true for multiple sclerosis (MS), a T cell-mediated demyelinating disease of the central nervous system (CNS) characterized by autoimmune responses to myelin proteins such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) (1,2,3,4). Epidemiological evidence strongly supports the hypothesis that many forms of human MS are initiated by a viral infection (5). The caveat of this hypothesis, which is strongly supported by epidemiological evidence, is that no particular virus or viruses have been consistently isolated from MS lesions. Thus, exploring the mechanisms by which infectious agents trigger autoimmune diseases is of great interest. Three mechanisms have been suggested to explain how a viral infection could lead to autoimmunity: viral superantigens that nonspecifically lead to activation of autoreactive T cells (6); molecular mimicry between the pathogen and self antigens which leads to direct activation of T cells induced against epitopes on the pathogen that are cross reactive with self epitopes (7); and epitope spreading evoked by virus-specific T cells that result in bystander damage to self tissue with consequent autoantigen release (8) or direct virus-induced release of self antigens (9), resulting in de novo activation of autoreactive T cells.

Keywords

Experimental Autoimmune Encephalomyelitis Myelin Basic Protein Myelin Oligodendrocyte Glycoprotein Epitope Spreading Myelin Destruction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Stephen D. Miller
    • 1
  • Todd N. Eagar
    • 1
  1. 1.Department of Microbiology-Immunology and Interdepartmental Immunobiology CenterNorthwestern University Medical SchoolChicagoUSA

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