INFLUENCE OF DELETION OF T-CELL RECEPTOR V-BETA GENES ON THE THEILERSS VIRUS MODEL OF MULTIPLE-SCLEROSIS

To determine the role of TCR V-beta genes in a model of multiple scler osis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V-beta chromosome. Congenic mice expressing the V-beta (a) [50% deletion of TCR V-beta] or V-beta(c) 70% deletion of TCR V-be ta] haplotype were generated in mice resistant [B10 (H-2(b))], interme diate [B10.K (H-2(k)), B10.RIII(H-2(r))] or susceptible [B10.S (H-2(s) ), and B10.Q (H-2(q))] to Theiler's virus induced demyelination. Delet ion of TCR V-beta genes (V-beta(a) or V-beta(c) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII -V-beta(c) developed prominent demyelination and 10- to 100-fold incre ase in virus-antigen expression in spinal cord compared to B10.RIII mi ce. No effect on the extent of demyelination was observed in B10.S-V-b eta(a) a B10.S-V-beta(c) or B10.Q-V-beta(c) mice. These experiments il lustrate the critical interactions between MHC, TCR, and background ge nes in susceptibility to immune-mediated disease.