Analysis of antibody responses to predominant linear epitopes of Theiler's murine encephalomyelitis virus

Using synthetic peptides, we have defined the major linear antibody epitopes of Theiler's murine encephalomyelitis virus (TMEV), i.e., A1A (VP1_12-25), A1Ba (VP1_146-160), A1Cb (VP1_262-276), A2A (VP2_2-16), A2B (VP2_165-179), and A3A (VP3_24-37). A time course study with either pooled or individual sera indicates that susceptible SJL mice intracerebrally infected with TMEV strongly and selectively recognize the A1Cb epitope of VP1, compared with resistant BALB/c or C57BL/6 mice, which broadly recognize most of the epitopes on the different capsid proteins. However, antibodies from SJL mice subcutaneously immunized with TMEV recognize primarily A1Ba, A1Cb, and A2A epitopes. A similar predominant recognition of the A1Cb epitope was found with antibodies from the cerebrospinal fluid of intracerebrally virus-infected SJL mice. Interestingly, a substantial level of antibodies against the A1Cb epitope in virus-infected SJL mice is of the immunoglobulin G2a subclass, in contrast to an undetectable level of this immunoglobulin G subclass in virus-immunized SJL mice. The level of in vitro viral neutralization by antibodies did not correlate with the clinical signs. Antibodies to A1Cb, A2A, and A2B were able to neutralize viral plaque formation in vitro, while antibodies to A3A, A1A, and A1Ba were not.