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

Immunology. 2013 Dec;140(4):456-64. doi: 10.1111/imm.12155.

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.

Keywords: C57BL/6; epitope; experimental autoimmune encephalomyelitis; mouse; multiple sclerosis; peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Central Nervous System / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Epitope Mapping
  • Epitopes*
  • Female
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein / deficiency
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Peptide Fragments / immunology*
  • Protein Structure, Tertiary
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Epitopes
  • Mog protein, mouse
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments