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The encephalitogenic, human myelin oligodendrocyte glycoprotein-induced antibody repertoire is directed toward multiple epitopes in C57BL/6-immunized mice.

Abstract
Although Abs specific for myelin oligodendrocyte glycoprotein (MOG) have been detected in patients with multiple sclerosis (MS), their contribution to pathogenesis remains poorly understood. Immunization of C57BL/6 mice with recombinant human MOG (hMOG) results in experimental autoimmune encephalomyelitis involving MOG-specific, demyelinating Abs. This model is therefore informative for understanding anti-MOG humoral responses in MS. In the current study, we have characterized the hMOG-specific Ab repertoire in immunized C57BL/6 mice using both in vitro and in vivo approaches. We demonstrate that hMOG-specific mAbs are not focused on one specific region of MOG, but instead target multiple epitopes. Encephalitogenicity of the mAbs, assessed by the ability of the mAbs to exacerbate experimental autoimmune encephalomyelitis in mice, correlates with the activity of the mAbs in binding to CNS tissue sections, but not with other in vitro assays. The targeting of different MOG epitopes by encephalitogenic Abs has implications for disease pathogenesis, because it could result in MOG cross linking on oligodendrocytes and/or immune complex formation. These studies reveal several novel features concerning pathogenic, humoral responses that may have relevance to human MS.
AuthorsPankaj Bansal, Tarique Khan, Uta Bussmeyer, Dilip K Challa, Rafal Swiercz, Ramraj Velmurugan, Raimund J Ober, E Sally Ward
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 3 Pg. 1091-101 (Aug 01 2013) ISSN: 1550-6606 [Electronic] United States
PMID23817425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Epitopes
  • MOG protein, human
  • Myelin-Oligodendrocyte Glycoprotein
Topics
  • Animals
  • Antibodies, Monoclonal (immunology)
  • Encephalomyelitis, Autoimmune, Experimental (immunology)
  • Epitopes (immunology)
  • Female
  • Humans
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis (immunology)
  • Myelin-Oligodendrocyte Glycoprotein (administration & dosage, immunology)
  • Oligodendroglia (immunology)
  • Surface Plasmon Resonance

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