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) patients has drawn attention to MBP isoforms harboring that peptide as candidate autoantigens. Previously, immunological studies in MS had almost exclusively used the more abundant 18.5 kDa isoform of MBP, which does not contain the exon 2 peptide. Investigations of experimental allergic 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 peptide in the SJL/J mouse. Evidence for increased expression of exon 2-containing isoforms during remyelination in mouse CNS suggested that exon 2-sensitized T cells, with encephalitogenic capacity, might be important in the perpetuation of relapsing EAE (rEAE). Our experiments have demonstrated that exon 2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by the adoptive transfer of exon 2-sensitized lymphocytes. Furthermore, the disease could be accentuated by the transfer of short-term exon 2-reactive lines or by a combination of adoptive transfer and antigenic challenge with exon 2 peptide. The immunodominant epitope(s) appeared to localize to the segment bordered by amino acids 59-85.
Segal
B M
BM
Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892.
Raine
C S
CS
McFarlin
D E
DE
Voskuhl
R R
RR
McFarland
H F
HF
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000939:Epitopes; D005091:Exons; D005260:Female; D005796:Genes; D006168:Guinea Pigs; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics* / Q000276:immunology*; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments