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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 16, 2014
Myelin-associated oligodendrocytic basic protein: identification of an encephalitogenic epitope and association with
A Holz1, B Bielekova, R Martin
1Viral-Immunobiology Laboratory, Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. aholz@scripps.edu
Abstract:
Myelin-associated oligodendrocytic basic protein (MOBP) is an abundant myelin constituent expressed exclusively by oligodendrocytes, the myelin-forming cells of the CNS. We report that MOBP causes experimental allergic encephalomyelitis and is associated with multiple sclerosis. First, we note that purified recombinant MOBP inoculated into SJL/J mice produces CNS disease. Tests of overlapping peptides spanning the murine MOBP molecule map the encephalitogenic site to amino acids 37-60. MOBP-induced experimental allergic encephalomyelitis shows a severe clinical course and is characterized by a prominent CD4+ T lymphocyte infiltration and a lesser presence of CD8+ T cells and microglia/macrophages around vessels and in the white matter of the CNS. Second, PBL obtained from patients with relapsing/remitting multiple sclerosis mount a proliferative response to human MOBP, especially at amino acids 21-39. This response equals or exceeds the response to myelin basic protein and an influenza virus hemagglutinin peptide, both serving as internal controls. Thus, a novel myelin Ag, MOBP aa 37-60, plays a role in rodent autoimmune CNS disease, and its human MOBP counterpart is associated with the human demyelinating disease multiple sclerosis.
Insights
Myelin-associated oligodendrocytic basic protein (MOBP) triggers experimental allergic encephalomyelitis in mice. MOBP is also linked to human multiple sclerosis, suggesting its role in autoimmune central nervous system diseases.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Central Nervous System (CNS) Research
Background:
- Myelin-associated oligodendrocytic basic protein (MOBP) is a key component of CNS myelin, produced by oligodendrocytes.
- Oligodendrocytes are crucial for myelin formation in the CNS.
Purpose of the Study:
- To investigate the role of MOBP in experimental allergic encephalomyelitis (EAE) and its association with multiple sclerosis (MS).
- To identify specific encephalitogenic regions of MOBP.
Main Methods:
- Induction of EAE in SJL/J mice using purified recombinant MOBP.
- Mapping of the encephalitogenic site using overlapping MOBP peptides.
- Assessment of T cell and glial cell infiltration in the CNS.
- Analysis of peripheral blood lymphocyte (PBL) proliferative responses to human MOBP in MS patients.
Main Results:
- Purified MOBP induced severe EAE in mice, characterized by CD4+ T cell infiltration.
- The encephalitogenic site in mice was mapped to amino acids 37-60 of MOBP.
- PBL from MS patients showed significant proliferative responses to human MOBP, particularly to amino acids 21-39.
Conclusions:
- A novel myelin antigen, MOBP amino acids 37-60, is implicated in rodent autoimmune CNS disease.
- The human counterpart of MOBP is associated with the human demyelinating disease, multiple sclerosis.
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