Diversity and structure of human T cell receptor δ chain genes in peripheral blood γ/δ-bearing T lymphocytes

Abstract

We have investigated the diversity and repertoire of human TCR δ chain variable gene segments in the human peripheral blood CD4- CD8- (double-negative) population, using rearrangement and expression studies and sequence analyses. 20 TCR δDNA clones were derived from the RNA of bulk-cultured double-negative T cells and their nucleotide sequences determined. These clones can be classified into six different V(δ) subfamilies. The distribution, however, was uneven in these cells, with 16 of 20 being derived from the V(δ)1 (9) and V(δ)2 (7) subfamilies. The remaining subfamilies, V(δ)3, V(δ)4, V(δ)5, and V(δ)6, were only represented by one clone each. The majority of these subfamilies seem to consist of a single member, in contrast with the closely linked V(α) subfamilies, which, in most cases, consist of multiple members. Our findings suggest that only a limited number of V(δ) genes are used in human peripheral blood double-negative T cells and that two major V(δ) subfamilies (V(δ)1 and V(δ)2) are used more frequently. Sequence comparison of our cDNA clones to V(α) clones indicates that there is no overlap in usage of V(α) and V(δ) gene segments, except for the V(δ)4 (V(α)6) subfamily. Comparison of the different V(δ) sequences suggests that the majority of the sequence diversity is concentrated in the junctions between V, D, and J segments and results from extensive N region diversity.