Structural requirements for initiation of cross-reactivity and CNS autoimmunity with a PLP139-151 mimic peptide derived from murine hepatitis virus

J. Ludovic Croxford, Anne M. Ercolini, Mathew DeGutes, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

MS is an autoimmune CNS demyelinating disease in which infection appears to be an important pathogenic factor. Molecular mimicry, the cross-activation of autoreactive T cells by mimic peptides from infectious agents, is a possible explanation for infection-induced autoimmunity. Infection of mice with a non-pathogenic strain of Theiler's murine encephalomyelitis virus (TMEV) engineered to express an epitope from Haemophilus influenzae (HI) sharing 6/13 amino acids with the dominant proteolipid protein (PLP) epitope, PLP139-151, can induce CNS autoimmune disease. Here we demonstrate that another PLP139-151 mimic sequence derived from murine hepatitis virus (MHV) which shares only 3/13 amino acids with PLP139-151 can also induce CNS autoimmune disease, but only when delivered by genetically engineered TMEV, not by immunization with the MHV peptide. Further, we demonstrate the importance of proline at the secondary MHC class II contact residue for effective cross-reactivity, as addition of this amino acid to the native MHV sequence increases its ability to cross-activate PLP139-151-specific autoreactive T cells, while substitution of proline in the HI mimic peptide has the opposite effect. This study describes a structural requirement for potential PLP139-151 mimic peptides, and provides further evidence for infection-induced molecular mimicry in the pathogenesis of autoimmune disease.

Original languageEnglish (US)
Pages (from-to)2671-2680
Number of pages10
JournalEuropean Journal of Immunology
Volume36
Issue number10
DOIs
StatePublished - Oct 2006

Keywords

  • Autoimmune disease
  • Central nervious system
  • Molecular mimicry
  • Multiple sclerosis
  • Proteolipid protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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