Cloning of the gene encoding the δ subunit of the human T-cell receptor reveals its physical organization within the α-subunit locus and its involvement in chromosome translocations in T-cell malignancy

By taking advantage of 'chromosomal walking' techniques, we have obtained clones that encompass the T-cell receptor (TCR) δ-chain gene. We analyzed clones spanning the entire J(α) region extending 115 kilobases 5' of the TCR α-chain constant region and have shown that the TCR δ-chain gene is located over 80 kilobases 5' of C(α). TCR δ-chain gene is rearranged in the γ/δ-expressing T-cell line Peer and is delected in α/β-expressing T-cell lines. Sequence analysis of portions of this genomic region demonstrates its identity with previously described cDNA clones corresponding to the C(δ) and J(δ) segments. Furthermore, we have analyzed a t(8;14)-(q24;q11) chromosome translocation from a T-cell leukemia and have shown that the J(δ) segment is rearranged in cells deriving from this tumor and probably directly involved in the translocation. Thus, the newly cloned TCR δ chain is implicated in the genesis of chromosome translocations in T-cell malignancies carrying cytogenetic abnormalities of band 14q11.