title: Novel pathogenic epitopes of myelin oligodendrocyte glycoprotein induce experimental autoimmune encephalomyelitis in C57BL/6 mice.
abstract: Myelin oligodendrocyte glycoprotein (MOG), a minor protein of the central nervous system myelin, is recognized as a potential target in multiple sclerosis and neuromyelitis optica. The extracellular domain of MOG is commonly used in a wide range of mouse strains and other animals to induce experimental autoimmune encephalomyelitis (EAE), an autoimmune animal model of multiple sclerosis, because it is a target for antibody-mediated attack. Previous studies, using selected peptides, have indicated that MOG(35-55) peptide is an encephalitogenic epitope in C57BL/6 (H-2(b)) mice. A more systematic analysis of both T-cell and B-cell responses following immunization of C57BL/6 mice with either recombinant extracellular mouse MOG protein (1-116) or with overlapping peptides spanning the whole sequence of MOG, before assessment of responses to 15 mer and 23 mer peptides was undertaken. The studies identified T-cell responses within the MOG(35-55) (extracellular domain) but also two new immunogenic and encephalitogenic T-cell epitopes within residues MOG(113-127), MOG(120-134) (localized in the transmembrane region) and MOG(183-197) (in the second hydrophobic MOG domain). In addition, residue MOG(113-127) was found to be a B-cell epitope, suggesting that this may be a useful adjunct for the induction of EAE as well as for immunological studies in C57BL/6 mice, which are increasingly being used to study immune function through the use of transgenic and gene knockout technology.
authors.affiliation: ICM - Hôpital Pitié-Salpêtrière, INSERM UMRS 975/UPMC/CNRS UMR7225, Paris, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Delarasse
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D000939:Epitopes; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments
keywords: C57BL/6; epitope; experimental autoimmune encephalomyelitis; mouse; multiple sclerosis; peptide