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.