Differential induction of experimental autoimmune encephalomyelitis by myelin basic protein molecular mimics in mice humanized for HLA-DR2 and an MBP85-99-specific T cell receptor

Maria T. Greene, Anne M. Ercolini, Mathew DeGutes, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Multiple sclerosis (MS) is a chronic autoimmune neurological disease characterized by infiltration of peripheral inflammatory cells to the central nervous system (CNS) and demyelination of CNS white matter. Epidemiological evidence suggests a possible infectious trigger. One potential mechanism by which an infectious agent may trigger MS is via molecular mimicry wherein T cells generated against foreign epitopes cross-react with self-myelin epitopes, such as myelin basic protein (MBP), with sufficient sequence similarity. It has been previously reported that an MBP85-99-reactive T cell clone derived from an MS patient cross-reacted with multiple bacterial-derived mimic peptides in vitro. We show that the same mimic peptides can induce clinical disease in two different strains of mice transgenic for both a human MBP85-99-specific TCR and HLA-DR2 (MHC II), albeit with different disease patterns - relapsing-remitting vs. monophasic. Interestingly, clinical disease correlates with CNS infiltration of CD4+ T cells and F4/80+ macrophages, but not with in vitro proliferative or cytokine responses of splenocytes in response to either MBP85-99 or its mimics.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalJournal of Autoimmunity
Volume31
Issue number4
DOIs
StatePublished - Dec 2008

Keywords

  • Autoimmunity
  • Experimental autoimmune encephalomyelitis
  • Molecular mimicry
  • Multiple sclerosis
  • Myelin basic protein
  • T cells
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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