Peptide epitopes of autoantigens make attractive candidates for immunotherapy of autoimmune diseases because of their potential to specifically suppress autoimmune reactions. Recently, """"""""peptide oligomers,"""""""" peptide epitopes alternating with a peptide spacer of fixed length, have been shown to dramatically enhance immunopotency compared to their monomeric counterparts. We propose to utilize such peptide oligomers (Peptimers(TM)) as the basis of a novel, antigen- specific approach to the treatment of autoimmune diseases. Our initial experiments will address the production and in vitro testing of purified peptide oligomers composed of myelin basic protein (MBP) amino acid residues 84-102 and proteolipid protein amino acid residues 139-151. The former has been implicated in multiple sclerosis (MS) and the latter has been used to induce a chronic form of experimental allergic encephalomyelitis (EAE; an animal model of MS) in rodents. Peptide oligomers from 4- to 28- epitopes, joined by peptide spacers, will be tested for their potential to induce tolerance as demonstrated by in vitro assays using T-cell clones isolated from MS patients and from rodents with EAE.
