DISTAL V-BETA PROMOTERS TRANSCRIBE NOVEL T-CELL RECEPTOR-BETA TRANSCRIPTS IN EARLY DEVELOPMENT

The transcriptional activation of germline T-cell receptor (TCR) and i mmunoglobulin (Ig) genes has been proposed to promote the rearrangemen t of these genes. Here we report the identification of distal TCR prom oters (PDs), located upstream of the previously characterized promoter s in the mouse V-beta 5.1 and V-beta 8.1 gene segments, that are activ e in germline TCR genes in fetal thymus and liver in vivo. We also ide ntified an immature T-cell clone, SL12.4, that expresses both endogeno us 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 devel opment. Northern blot, RNase protection and reverse transcription-poly merase chain reaction (RT-PCR) analyses demonstrated that PDs are also transcribed from fully rearranged TCR genes in adult thymus, lymph no de, and spleen. Although the functional significance of this expressio n 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 regul ate the efficiency of TCR beta translation.