ASSOCIATION BETWEEN SUSCEPTIBILITY TO THEILERS-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 t hus, this system provides an excellent infectious animal model for stu dying MS. The virus-induced demyelination is immune mediated, and the genes involved in the immune response such as those for the T-cell rec eptor 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 susc eptibility, 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 demye lination is associated with restriction fragment length polymorphism r eflecting the T-cell receptor J beta 1-C beta 1 region rather than the V beta polymorphism. This association becomes stronger when the MHC h aplotype is considered in the linkage analysis. However, differences i n the T-cell receptor alpha-chain haplotype have no significant influe nce on the pathogenesis of TMEV-induced demyelination.