Use of a variable alpha region to create a functional T-cell receptor delta chain.

Abstract

Two categories of T-cell antigen-specific receptor have been described. Most mature T lymphocytes have, on their membrane, an antigen receptor consisting of alpha and beta subunits, while early T cells and thymocytes possess a heterodimeric receptor termed gamma-delta. The DS6 clone, isolated from the peripheral blood of a patient with immunodeficiency, is a CD3+, CD4-, CD8- human T-cell line that expresses the disulfide-linked form of the gamma-delta antigen receptor. The nucleotide sequence analysis of DS6 cDNA makes clear that its variable region is a member of an alpha variable-region gene family. We have cloned and sequenced the germ-line joining and variable regions used to create the DS6 delta mRNA. Comparison of these sequences does not show evidence of extensive somatic mutations. The major difference between the germ-line and the T-cell antigen receptor delta cDNA sequence is an insertion of three consecutive nucleotides between the variable and joining segments and is evocative of somatic diversification rather than of the use of a germ-line-encoded diversity region.