A T cell‐specific enhancer is located in a DNase I‐hypersensitive area at the 3′ end of the CD3‐delta gene.

During intrathymic differentiation, the genes coding for the T cell receptor/CD3 (TCR/CD3) complex are expressed in stages resulting in surface expression of competent receptors on the most mature T cells. The CD3‐delta, gamma and epsilon proteins, which are expressed intracellularly in the earliest detectable cells of T lineage, form the core of the TCR/CD3 complex. In the present investigation aimed at understanding the tissue specific expression of the murine CD3‐delta gene, a T cell specific DNase I hypersensitive site was found 0.6 kb downstream of the polyadenylation site of the gene. A 0.4 kb genomic fragment encompassing this hypersensitive site exhibited properties of a strictly T cell‐specific transcriptional enhancer which acts in a position‐ and orientation‐independent manner. However, the activity of the promoter region was not found to be T cell restricted. Within this novel T cell‐specific enhancer region, sequence motifs were found which are shared with the promoters of both the mouse and human CD3‐delta genes; in this region we also found sequence homologies to the enhancer core element of the thymotropic viruses SL3 and RadLV. These findings suggest that regulatory elements 3′ of the CD3‐delta gene are at least in part responsible for its exclusive expression in thymus‐derived lymphocytes.