The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat.
Using a highly purified recombinant protein, mMOG, we demonstrated that autoimmune responses to the N-terminal domain (a.a 1-125) of the myelin oligodendrocyte glycoprotein (MOG) induce an acute demyelinating variant of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Immunisation with 100 micrograms of mMOG in adjuvant at the base of the tail induced mild clinical disease in 9 of 11 animals (mean clinical score 1.1). The disease was characterised histopathologically by the presence of inflammation and focal demyelinating lesions in the central nervous system (CNS). Adoptive transfer experiments suggest that this inflammatory demyelinating pathology is mediated by synergy between a weakly encephalitogenic, MOG-specific T cell response and a demyelinating, MOG-specific autoantibody response. Using in vitro selected mMOG-reactive T cell lines, the encephalitogenic T cell response to this domain of MOG was found to recognise two distinct epitopes, MOG1-20 and MOG35-55; whereas ELISA demonstrated that the immunodominant B cell epitope was located within the amino acid sequence MOG1-25. However although active immunisation with synthetic peptides corresponding to the T cell epitopes, MOG1-20 or MOG35-55, induced an inflammatory response in the CNS, this was not associated with demyelination indicating that the demyelinating antibody response recognises other, possibly conformation dependent epitopes. This study unequivocally demonstrates that MOG-specific autoimmune responses are alone sufficient to induce a demyelinating disease of the CNS and supports the proposal that MOG may play an important role in the immunopathogenesis of multiple sclerosis.
Adelmann
M
M
Max-Planck Institute of Psychiatry, Department of Neuroimmunology, Martinsried, Germany.
Wood
J
J
Benzel
I
I
Fiori
P
P
Lassmann
H
H
Matthieu
J M
JM
Gardinier
M V
MV
Dornmair
K
K
Linington
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009836:Oligodendroglia / Q000737:chemistry*; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C000602291:myelin oligodendrocyte glycoprotein (1-125)