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Antibody response in Lewis rats injected with myelin oligodendrocyte glycoprotein derived peptides
M Ichikawa1, T G Johns, M Adelmann
1Neuroimmunology Laboratory, Faculty of Science and Technology, La Trobe University, Melbourne, Victoria, Australia.
Abstract:
Previous studies from our laboratory have demonstrated a predominant response to myelin oligodendrocyte glycoprotein (MOG) in patients with multiple sclerosis (MS) and showed that this molecule is able to induce in Lewis rats a chronic relapsing MS-like disease with extensive demyelination. To further study the possibility that MOG is a primary target antigen in MS, we have begun to investigate the encephalitogenicity and antibody response of different sequences of the extracellular domains of MOG in Lewis rats. We report that none of the synthetic peptides encompassing the MOG amino acid sequences 1-21, 67-87, 104-117 and 202-218 were encephalitogenic. In contrast, a single injection of MOG35-55 was able to induce severe neurological signs associated with inflammation and demyelination. All rats injected with MOG peptides 1-21, 35-55, 67-87 and 202-218 developed a high level of antibodies to their respective immunizing peptides as detected by ELISA and immunoblotting. Although all MOG peptide antisera reacted with immunoblots of native MOG separated under reducing conditions, only anti-MOG35-55 and anti-MOG202-218 antibodies reacted to native MOG, when tested under nonreducing conditions. These results indicate that the MOG35-55 peptide, which is found in the extracellular Ig V-like domain of MOG, is not only an encephalitogenic epitope but could also be an important determinant for initiating antibody-mediated demyelination. As indicated by the absence of reactivity to the other MOG peptides tested, as well as other central nervous system myelin proteins including myelin basic protein and proteolipid protein, the antibody response produced by MOG peptides is highly restricted.
Insights
Myelin oligodendrocyte glycoprotein (MOG) peptides were tested for their role in multiple sclerosis (MS) pathogenesis. MOG35-55 was found to be encephalitogenic, inducing MS-like disease and antibodies, suggesting its importance in demyelination.
Area of Science:
- Neuroimmunology
- Autoimmune diseases
- Demyelinating disorders
Background:
- Previous studies implicated myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis (MS).
- MOG induces experimental autoimmune encephalomyelitis (EAE) in Lewis rats, a chronic relapsing MS-like disease with demyelination.
Purpose of the Study:
- To investigate the encephalitogenic and antibody response to different extracellular MOG peptide sequences in Lewis rats.
- To determine if MOG is a primary target antigen in MS.
Main Methods:
- Synthetic peptides of MOG extracellular domains (1-21, 35-55, 67-87, 104-117, 202-218) were synthesized.
- Lewis rats were immunized with these peptides.
- Encephalitogenicity was assessed by neurological signs, inflammation, and demyelination.
- Antibody responses were measured using ELISA and immunoblotting under reducing and nonreducing conditions.
Main Results:
- MOG35-55 peptide induced severe neurological signs, inflammation, and demyelination in Lewis rats.
- Antibodies were generated against MOG peptides 1-21, 35-55, 67-87, and 202-218.
- Anti-MOG35-55 and anti-MOG202-218 antibodies reacted with native MOG under nonreducing conditions.
Conclusions:
- The MOG35-55 peptide is encephalitogenic and can initiate antibody-mediated demyelination.
- MOG35-55 is a key epitope in the pathogenesis of MOG-induced EAE.
- The antibody response to MOG peptides is highly restricted.