Single β³-amino acid substitutions to MOG peptides suppress the development of experimental autoimmune encephalomyelitis

Abstract

CD4(+) T-cells play a key role in the pathogenesis of multiple sclerosis (MS). Altered peptide ligands capable of modulating T-cell autoreactivity are considered a promising strategy for development of antigen-specific therapies for MS. Since peptides are inherently unstable, the current study explored single β-amino acid substitution as a means of stabilizing an epitope of myelin oligodendrocyte glycoprotein. β-Amino acid substitution at position 44, the major T-cell receptor contact residue, increased the half-life of active metabolites. Vaccination with one altered peptide, MOG44βF, conferred protection from EAE, decreased T-cell autoreactivity and pro-inflammatory cytokine production. Additional studies using MOG44βF in an oral treatment regimen, administered after EAE induction, also attenuated disease severity. Thus, altered peptides such as those reported here may lead to the development of novel and more specific treatments for MS.

Keywords: Altered peptide ligands; Beta-amino acid; Immunosuppressive; Multiple sclerosis; Myelin oligodendrocyte glycoprotein; Neuroinflammation.