Functional activation of myelin-specific T cells by virus-induced molecular mimicry

Julie K. Olson, Todd N. Eagar, Stephen D. Miller

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Molecular mimicry is the process by which T cells activated in response to determinants on an infecting microorganism cross-react with self epitopes, leading to an autoimmune disease. Normally, infection of SJL/J mice with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent CNS infection, leading to a chronic progressive, CD4+ T cell-mediated demyelinating disease. Myelin damage is initiated by T cell responses to virus persisting in CNS APCs, and progressive demyelinating disease (50 days postinfection) is perpetuated by myelin epitope-specific CD4+ T cells activated by epitope spreading. We developed an infectious model of molecular mimicry by inserting a sequence encompassing the immunodominant myelin epitope, proteolipid protein (PLP) 139-151, into the coding region of a nonpathogenic TMEV variant. PLP139-TMEV-infected mice developed a rapid onset paralytic inflammatory, demyelinating disease paralleled by the activation of PLP139-151-specific CD4+ Th1 responses within 10-14 days postinfection. The current studies demonstrate that the early onset demyelinating disease induced by PLP139-TMEV is the direct result of autoreactive PLP139-151-specific CD4+ T cell responses. PLP139-151-specific CD4+ T cells from PLP139-TMEV -infected mice transferred demyelinating disease to naive recipients and PLP139-151-specific tolerance before infection prevented clinical disease. Finally, infection with the mimic virus at sites peripheral to the CNS induced early demyelinating disease, suggesting that the PLP139-151-specific CD4+ T cells could be activated in the periphery and traffic to the CNS. Collectively, infection with PLP139-151 mimic encoding TMEV serves as an excellent model for molecular mimicry by inducing pathologic myelin-specific CD4+ T cells via a natural virus infection.

Original languageEnglish (US)
Pages (from-to)2719-2726
Number of pages8
JournalJournal of Immunology
Volume169
Issue number5
StatePublished - Sep 1 2002

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Molecular Mimicry
Theilovirus
Myelin Sheath
Demyelinating Diseases
Viruses
T-Lymphocytes
Infection
Epitopes
Immunodominant Epitopes
T-Lymphocyte Epitopes
Virus Diseases
Autoimmune Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Olson, J. K., Eagar, T. N., & Miller, S. D. (2002). Functional activation of myelin-specific T cells by virus-induced molecular mimicry. Journal of Immunology, 169(5), 2719-2726.

Functional activation of myelin-specific T cells by virus-induced molecular mimicry. / Olson, Julie K.; Eagar, Todd N.; Miller, Stephen D.

In: Journal of Immunology, Vol. 169, No. 5, 01.09.2002, p. 2719-2726.

Research output: Contribution to journalArticle

Olson, JK, Eagar, TN & Miller, SD 2002, 'Functional activation of myelin-specific T cells by virus-induced molecular mimicry', Journal of Immunology, vol. 169, no. 5, pp. 2719-2726.
Olson, Julie K. ; Eagar, Todd N. ; Miller, Stephen D. / Functional activation of myelin-specific T cells by virus-induced molecular mimicry. In: Journal of Immunology. 2002 ; Vol. 169, No. 5. pp. 2719-2726.
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