T-CELL RECEPTOR ALPHA-CHAIN GERMLINE GENE POLYMORPHISMS IN MULTIPLE-SCLEROSIS

It has been proposed that genetic predisposition to multiple sclerosis (MS) and other diseases with autoimmune features is conferred by T-cell receptor (TcR) genes in addition to HLA class II genes. Although a family study has suggested linkage of susceptibility to MS to TcR genes, reports of disease associations with restriction fragment length polymorphism (RFLP)-defined alleles of TcR genes have been difficult to confirm, including a report of association of MS with TcR beta-chain gene RFLPs. We report here the distribution of three sets of RFLPs of the TcR alpha-chain genes. Similar frequencies in patients and controls were observed for TaqI and BglII RFLPs of the TcR alpha constant segment (C(alpha)), the latter earlier reported to be associated with MS. A previously reported MS-associated PssI RFLP of the V(alpha)12 and C(alpha) gene segments could not be confirmed. Our results indicate that these seemingly polymorphic restriction fragments are possibly the results of incomplete enzymatic cleavage of DNA in the RFLP analysis. We conclude that no convincing evidence exists for the association of MS with RFLPs of the TcR alpha or beta chain genes.