The TCR ζ chain plays a significant role in the assembly of the receptor complex and in coupling antigen recognition to the untracellular signal transductlon apparatus. Since the ζ protein level is considered the limiting factor for receptor assembly in mature T cells, aberrant expression of the ζ, chain affects both receptor structure and function. To understand the regulatory mechanisms controlling ζ, gene expression, we characterized the 5' flanking region of the gene. Our analysis reveals the existence of at least three regions within the -784 to +121 fragment involved in the transcription of the ζ, gene in T cells: (i) the fragment from -216 to +121 contains the basal promoter; (ii) the sequence between -561 and -216 includes positive elements which confer strong transcriptional activity; and (iii) the region between -784 and -561 which contains negative element(s) that down-regulate ζ gene transcription. The entire 5' flanking region of the ζ, gene is functional in both T and fibroblast cell lines, although the transcriptional levels and the specific regions required for maximal activity differ between the two cell types. Maximal transcriptional activity is achieved when T cells are stimulated simultaneously via the TCR and with PMA. The transcriptional activity of the ζ gene can be induced by PMA alone in T cells but not in fibroblasts, suggesting that this effect is mediated by T cell-specific factors. We also demonstrate that upregulation of the transcriptional activity induced by the different stimuli is consistent with increased expression of ζ, mRNA, pointing to the possibility that signal transduction events initiated during T cell activation may be involved in controlling ζ gene expression.
Bibliographical noteFunding Information:
zion Levy, Danielle Melloul and Steve Caplan for critical reading of this manuscript. V\fe also thank Alexandra Mahler for her editorial assistance. This work was supported by the CONCERN Foundation of Los Angeles, by the Israel Academy of Sciences and Humanities, and by the Israel Cancer Research Foundation.
We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center. We thank Rachel Ehriich, Ben
- T cell
- ζ mRNA