Induction and suppression of an autoimmune disease by oligomerized t cell epitopes: Enhanced in vivo potency of encephalitogenic peptides

Kirsten Falk, Olaf Rötzschke, Laura Santambrogio, Martin E. Dorf, Celia Brosnan, Jack L. Strominger

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

T cell epitope peptides derived from proteolipid protein (PLP139-151) or myelin basic protein (MBP86-100) induce experimental autoimmune encephalomyelitis (EAE) in 'susceptible' strains of mice (e.g., SJL/J). In this study, we show that the encephalitogenic effect of these epitopes when injected subcutaneously in complete Freund's adjuvant was significantly enhanced if administered to the animal in a multimerized form as a T cell epitope oligomer (i.e., as multiple repeats of the peptide epitope, such as 16-mers). Oligomer-treated SJL/J mice developed EAE faster and showed a more severe progression of the disease than animals treated with peptide alone. In addition, haplotype-matched B10.S mice, 'resistant' to EAE induction by peptide, on injection of 16-mers developed a severe form of EAE. Even more striking, however, was the dramatic suppression of incidence and severity of the disease, seen after single intravenous injections of only 50 μg of the pLP139-151 16-mer, administered to SJL/J mice 7 d after the induction of the disease. Although relapse occurred at about day 45, an additional injection several days before that maintained the suppression. Importantly, the specific suppressive effect of oligomer treatment was also evident if EAE was induced with spinal cord homogenate instead of the single peptide antigen. By contrast, the PLP139-151 peptide accelerated rather than retarded the progression of disease.

Original languageEnglish (US)
Pages (from-to)717-730
Number of pages14
JournalJournal of Experimental Medicine
Volume191
Issue number4
DOIs
StatePublished - Feb 21 2000

Keywords

  • Anergy
  • Apoptosis
  • Experimental autoimmune encephalomyelitis
  • High zone tolerance
  • Multimer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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