Novel pathogenic epitopes of myelin oligodendrocyte glycoprotein induce experimental autoimmune encephalomyelitis in C57BL/6 mice

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.