Distal V beta promoters transcribe novel T-cell receptor-beta transcripts in early development.

Abstract

The transcriptional activation of germline T-cell receptor (TCR) and immunoglobulin (Ig) genes has been proposed to promote the rearrangement of these genes. Here we report the identification of distal TCR promoters (PDs), located upstream of the previously characterized promoters in the mouse V beta 5.1 and V beta 8.1 gene segments, that are active in germline TCR genes in fetal thymus and liver in vivo. We also identified an immature T-cell clone, SL12.4, that expresses both endogenous and transfected PDs in a regulated manner in vitro. We propose that the transcription of these distal promoters in germline TCR genes may be important for inducing TCR gene rearrangements during T-cell development. Northern blot, RNase protection and reverse transcription-polymerase chain reaction (RT-PCR) analyses demonstrated that PDs are also transcribed from fully rearranged TCR genes in adult thymus, lymph node, and spleen. Although the functional significance of this expression is not known, our sequence analysis of the 5' leader in PD-derived V beta 5.1 and V beta 8.1 transcripts revealed the presence of several open reading frames (ORFs) that may encode novel polypeptides or regulate the efficiency of TCR beta translation.