Sequence and organization of the diversity, joining, and constant region genes of the human T-cell δ-chain locus

Abstract

In this paper we describe the genomic organization and sequence of the human T-cell receptor δ-chain diversity, joining, and constant genes. There is one δ-chain constant region gene (C(δ)) located ~85 kilobases (kb) upstream of the α-chain constant region. The δ-chain constant region consists of four exons, whose organization is very similar to that of the C(α) exons, suggesting that C(α) and C(δ) may have arisen from a gene duplication event. The first exon encodes most of the extracellular constant domain, the second encodes a hinge-like region, and the third encodes the entire transmembrane segment and intracytoplasmic portion, whereas the last exon contains exclusively 3' untranslated sequences. Three joining segments, J(δ)1, J(δ)2, and J(δ)3, are found ~12, ~5.7, and ~3.4 kb upstream of the first exon of C(δ). Two functional diversity gene segments, D(δ)1 and D(δ)2, which can be productively translated in all three reading frames, are found 1 and 9.6 kb upstream of J(δ)1. The presence of two D(δ) with such potential for diversity may offset the limited repertoire of the J(δ) and V(δ) genes. The spacer distribution in the recombinational signals flanking D(δ) and J(δ) segments allows recombination with V(α) gene segments; however, examination of δ-chain messages does not indicate that this is the case, suggesting that the δ chain uses unique variable gene segments and raising the question as to the reasons for this phenomenon.