Analysis of serum antibody levels to linear epitopes during the course of Theiler's virus-induced demyelination

Theiler's Murine Encephalomyelitis Virus (TMEV) induces immunemediated demyelination and this system serves as a viral model for multiple sclerosis. It is well established that cell-mediated immunity plays a critical role in the immune-mediated pathogenicity of the virus-induced demyelinating disease. However, no correlation can yet be drawn between antibody response to viral epitopes and the progression of the disease. Previously, we have identified 6 major linear antibody epitopes on the viral capsid proteins (J. Virol. 94). The pattern of antibodies produced against the individual epitopes was different between susceptible and resistant mouse strains. In this study, we have utilized fusion proteins containing individual viral capsid proteins and synthetic peptides containing the above linear antibody epitopes to determine the potential role of antibody response to the course of viral demyelination. Preimmunization of susceptible SJL mice with VP1 and VP2 fusion proteins, but not VP3, resulted in the protection of mice from subsequent infection with TMEV. Interestingly, the levels of antibodies against VP1 and VP2 epitopes other than A1C (residues 263-276) correlated with the protection. However, the level of antibodies to A1C was proportional to the progression of viral demyelinating disease. Further experiment in combination with synthetic peptides containing individual epitopes confirmed the role of epitopespecific antibodies for the protection and excluded the potential role of T cells. The mechanisms involved in the increase in the preferential antibody response to A1C is not yet clear.