Structure and rearrangement of the T cell receptor J alpha locus in T cells and leukemic T cell lines

Abstract

The vast majority of T cells express an antigen receptor (TcR) composed of an alpha/beta heterodimer. The alpha and beta chains are encoded for by a set of variable (V), joining (J) and constant (C) region genes. Unlike the J genes of the beta chain which are limited in number and are clustered close to the constant region, the J alpha genes are spread over an 85-kilobase DNA region, upstream of the C alpha gene. We have isolated the complete J alpha locus, bounded on the 5' side by the C sequence of the delta gene and on the 3' side by the C sequence of the alpha gene. The experiments described here demonstrate that the J gene segments extend 75 kb 5' of C alpha and participate equally in generating the diversity of the alpha chain in peripheral T cells. Similarly, in leukemic T cell lines, rearrangements occurred over the entire locus and involved both alleles. Densitometry data suggest that in most peripheral T cells both alleles also are rearranged; thus, allelic exclusion in the alpha locus does not occur at the level of rearrangement. In three cell lines, an identical rearrangement has occurred on one allele in a region located 10 kb from the 5' end of the locus.