DIVERSITY OF NOVEL RECOMBINING ELEMENTS SUGGESTS DEVELOPMENTALLY PROGRAMMED EXPRESSION OF THE T-CELL RECEPTOR ALPHA/DELTA-LOCUS

During fetal ontogeny, the first wave of gamma-delta T lymphocytes appears in the thymus at day 14 of gestation assembling predominantly T cell receptors (TcR) with V(gamma)3 and V(delta)1. To identify V(delta) gene segments that are transcribed at day 16, subsequent to the first wave of V(delta)1 expression, delta-chain cDNA was amplified by the anchored polymerase chain reaction with single-sided specificity for C(delta). Unexpectedly, most of the cDNA clones do not contain V gene segments. In some cDNA clones an alternative splice from the leader exon to the C(delta) exon has deleted the whole variable region exon. In other cDNA clones, multiple non-V-like elements are juxtaposed to the D(delta)2 and J(delta)1 gene segments. A large number of these diverse elements appear to be rearranged in fetal thymocytes, bringing V(alpha) gene segments located upstream of the recombining element into proximity to the J(alpha) locus. It is proposed that these rearrangements make irreversible the commitment to the TcR alpha-beta-lineage and determine a programmed read out of different clusters of V(alpha) gene segments.