The CD3 delta gene encodes multiple transcripts regulated by transcriptional and post-transcriptional mechanisms

Abstract

CD3 is a multi-subunit complex of proteins noncovalently associated with the T cell receptor (TcR) for antigen. Considerable evidence indicates a role for CD3 molecules in the transduction of activation signals in T cells. The murine CD3 delta gene encodes a 0.7-kb transcript present in mature T cells. Here we report the characterization of several additional CD3 delta transcripts; two nuclear transcripts, 4-4.5 kb in size, and two predominamtly cytoplasmic transcripts of 1.5 kb and 2.5 kb. Both T lymphoma cell lines and normal thymocytes express the 1.5-kb and 2.5-kb CD3 delta transcripts. These cytoplasmic transcripts have long 3'-untranslated sequences which extend beyond the polyadenylation site of the predominant 0.7-kb transcript. The protein synthesis inhibitor cycloheximide (CHX) increases the expression of all three cytoplasmic CD3 delta transcripts, indicating that their level of expression may be regulated by a labile inhibitor protein(s). The CHX elicited increase in CD3 delta mRNA appears to result from post-transcriptional events since the rate of CD3 delta gene transcription remains constant. In contrast to CHX, the calcium ionophore A23187 increases the rate of CD3 delta gene transcription and, like CHX, also increases the level of cellular CD3 delta mRNA. The immunosuppressive agent cyclosporin A inhibits A23187-mediated stimulation of transcription, but has no effect on the CHX-mediated induction of CD3 delta mRNA. We conclude that both transcriptional and post-transcriptional mechanisms can regulate the amount of all three cytoplasmic CD3 delta transcripts.