FURTHER LOCALIZATION OF A MULTIPLE-SCLEROSIS SUSCEPTIBILITY GENE ON CHROMOSOME-7Q USING A NEW T-CELL RECEPTOR BETA-CHAIN DNA POLYMORPHISM

Multiple sclerosis (MS) has been associated with particular HLA haplotypes and has recently been reported to also be associated with the T cell receptor (TCR) beta-chain complex. We have tried to determine the source of the TCR-beta/MS association by exploiting the pattern of linkage disequilibrium within the TCR-beta complex. We describe a new DNA polymorphism with the TCR variable region gene segment V-beta-15 which appears to localize between the constant region and V-beta-11. When the distribution of V-beta-11 - V-beta-15 haplotypes in MS patients was compared to healthy controls, the strength of the V-beta-11 - V-beta-15 MS association (p = 0.107) was much less than the MS association with the adjacent V-beta-8 - V-beta-11 haplotype (p = 0.0010). On this basis we exclude an MS susceptibility gene telomeric to V-beta-11. The reported MS association with the TCR-beta gene complex therefore does not appear to be due to genes within the diversity, joining, or constant region but more likely involves a specific gene(s) within the variable region.