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

T cell epitope peptides derived from proteolipid protein (PLP139-151) or my elin basic protein (MBP86-100) induce experimental autoimmune encephalomyel itis (EAE) in "susceptible" strains of mice (e.g., SJL/J). In this study, w e show that the encephalitogenic effect of these epitopes when injected sub cutaneously in complete Freund's adjuvant was significantly enhanced if adm inistered 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). Oligo mer-treated SJL/J mice developed EAE faster and showed a more severe progre ssion of the disease than animals created 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, ho wever, was the dramatic suppression of incidence and severity of the diseas e, seen after single intravenous injections of only 50 mu g of the PLP139-1 51 16-mer, administered to SJL/J mice 7 d after the induction of the diseas e. Although relapse occurred at about day 45, an additional injection sever al days before that maintained the suppression. Importantly, the specific s uppressive effect of oligomer treatment was also evident if EAE was induced with spinal cord homogenate instead of the single peptide antigen. By cont rast, the PLP139-151 peptide accelerated rather than retarded the progressi on of disease.