Further localization of a multiple sclerosis susceptibility gene on chromosome 7q using a new T cell receptor beta-chain DNA polymorphism

Abstract

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) β-chain complex. We have tried to determine the source of the TCR-β/MS association by exploiting the pattern of linkage disequilibrium within the TCR-β complex. We describe a new DNA polymorphism with the TCR variable region gene segment V β15 which appears to localize between the constant region and V β11. When the distribution of V β11–V β15 haplotypes in MS patients was compared to healthy controls, the strength of the V β11–V β15 MS association ( p = 0.107) was much less than the MS association with the adjacent V β8–V β11 haplotype ( p = 0.0010). On this basis we exclude an MS susceptibility gene telomeric to V β11. The reported MS association with the TCR-β 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.