Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors

Abstract

We have cloned three pairs of rearranged and germ-line variable region (V beta) genes of the beta chain of the human T-cell receptor from the cell lines ATL2, ATL12, and MT-1 of patients with adult T-cell leukemia (ATL). The pairs were derived from the same (for ATL2 and ATL12) and different (for MT-1) individuals. Comparison of the nucleotide sequences showed no somatic mutation in V beta X ATL2 and beta X ATL12-2. Although one nucleotide change was found in V beta X MT1-1, the possibility of polymorphism was not excluded. These results indicate that the frequency of somatic mutation in the V beta gene of the T-cell receptor is 1/10th or less than that in the immunoglobulin gene. Both alleles of the rearranged T-cell receptor gene were analyzed for ATL12 and MT-1. In both, only one of the two rearranged J beta alleles was an active variable-diversity-joining (V-D-J) complex. The results suggest that allelic exclusion occurs in the T-cell receptor gene.