Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor β chain

Abstract

The organization and sequences of the human β-chain T-cell receptor diversity, joining, and constant region segments are described. The β chain of the human T-cell receptor, analogous to the mouse counterpart, consists of two distinct constant region genes ~ 10 kilobases apart. The two constant region genes, C(β1) and C(β2), are very similar not only in sequence but also in genomic organization. The coding sequences of each of these C(β) constant region genes are divided into four exons. The first two exons encode most of the extracellular constant domain. The third exon encodes a major part of the presumed transmembrane portion, and the last exon contains the cytoplasmic coding sequence as well as 3' untranslated sequences. Except for a stretch of ~ 95 highly conserved nucleotides extending 3' of the first exon of the C region genes, little homology can be found between the intron sequences of C(β1) and C(β2). A small cluster of joining region (J(β)) gene segments is located ~ 5 kilobases upstream of each of these two constant regions. The first cluster, J(β1), contains six functional J gene segments while the second, J(β2), contains seven functional J gene segments. In addition, diversity region (D(β)) gene segments are located ~ 600 base pairs upstream of each J(β). Recombinational signals containing higher conserved heptamer and nonamer sequences separated by 12 or 23 bases are found adjacent to all of these D(β) and J(β) gene segments. These signal sequences are thought to be involved in the somatic recombination processes. These results indicate that what appears to be a gene duplication event giving rise to these two distinct regions must have arisen a long time ago in the evolution of this gene locus.