Association between susceptibility to Theiler's virus-induced demyelination and T-cell receptor J beta 1-C beta 1 polymorphism rather than V beta deletion

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mouse strains after intracerebral inoculation. The clinical symptoms and histopathology of the central nervous system appear to be similar to those of human multiple sclerosis (MS), and thus, this system provides an excellent infectious animal model for studying MS. The virus-induced demyelination is immune mediated, and the genes involved in the immune response such as those for the T-cell receptor beta-chain and major histocompatibility complex (MHC) haplotypes are known to influence disease susceptibility. To define whether the T-cell receptor J beta-C beta or v beta genes are associated with susceptibility, we have analysed F-2 mice from crosses of susceptible SJL/J (V beta(a)-JC beta(a)) mice and resistant C57L (V beta(a)-JC beta(b)) mice. Our results indicate that susceptibility to TMEV-induced demyelination is associated with restriction fragment length polymorphism reflecting the T-cell receptor J beta 1-C beta 1 region rather than the V beta polymorphism. This association becomes stronger when the MHC haplotype is considered in the linkage analysis. However, differences in the T-cell receptor alpha-chain haplotype have no significant influence on the pathogenesis of TMEV-induced demyelination.