EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS INDUCED BY THE PEPTIDE ENCODED BY EXON-2 OF THE MBP GENE, A PEPTIDE IMPLICATED IN REMYELINATION

The discovery of T lymphocytes reactive to the peptide encoded by exon 2 of the myelin basic protein (MBP) gene in multiple sclerosis (MS) p atients has drawn attention to MBP isoforms harboring that peptide as candidate autoantigens. Previously, immunological studies in MS had al most exclusively used the more abundant 18.5 kDa isoform of MBP, which does not contain the exon 2 peptide. Investigations of experimental a llergic encephalomyelitis (EAE) have also focussed on the 18.5 kDa MBP isoform and its peptides. Since EAE is an animal model widely used to study MS, we examined the encephalitogenic potential of exon 2 peptid e in the SJL/J mouse. Evidence for increased expression of exon 2-cont aining isoforms during remyelination in mouse CNS suggested that exon 2-sensitized T cells, with encephalitogenic capacity, might be importa nt in the perpetuation of relapsing EAE (rEAE). Our experiments have d emonstrated that exon 2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by the adoptive transfer of exon 2-sensi tized lymphocytes. Furthermore, the disease could be accentuated by th e transfer of short-term exon 2-reactive lines or by a combination of adoptive transfer and antigenic challenge with exon 2 peptide. The imm unodominant epitope(s) appeared to localize to the segment bordered by amino acids 59-85.