Human CD3-ε gene contains three miniexons and is transcribed from a non-TATA promoter

The antigen receptor of the T lymphocyte consists of two variable T-cell receptor chains (either TCR-α, TCR-β or TCR-γ, TCR-δ) noncovalently linked to four different invariant membrane proteins (CD3-γ, CD3-δ, CD3-ε, and the CD3-ζ homodimer). The CD3 genes are expressed early in thymocyte development, preceding the rearrangement and expression of the T-cell receptor genes. Here we report the isolation and structural analysis of the human CD3-ε gene. The gene consisted of nine exons. Three exons, encoding the junction of leader peptide and mature protein, were extremely small (21, 15, and 18 base pairs, respectively). The murine gene contained only two such miniexons, the sequences of which were not homologous to those of the three human miniexons. But from comparisons of intron sequences the regions surrounding the human miniexons III and IV appeared to be closely related to those surrounding the murine miniexons III and IV. The most-3' miniexon in the human gene (IVa) had no murine counterpart and appeared not to duplicate any of the other miniexons. Sequence analysis of CD3-ε cDNA clones isolated from four independent libraries gave no evidence for alternative use of these miniexons. Like CD3-δ, the CD3-ε gene was transcribed from a weak, nontissue-specific, TATA-less promoter. Pulsed-field electrophoresis showed that the human CD3-ε gene was separated from the CD3-γ, CD3-δ gene pair by at least 30 kilobases, but by no more than 300 kilobases.