THE SAME TARGET SEQUENCES ARE DIFFERENTIALLY IMPORTANT FOR ACTIVATION OF THE INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN GENE IN 2 DISTINCT T-CELL LINES

High-affinity receptors for interleukin 2 (IL-2) are expressed on T cells following activation. These receptors are composed of both α and β chains. Expression of α chains and, therefore, expression of high-affinity receptors are critically regulated at the level of transcription initiation. We have further dissected the regulatory elements involved in controlling transcription of the IL-2 receptor α-chain (IL-2Rα) gene. The IL-2Rα promoter contains a κB site and binding sites for additional nuclear factors within a 50-base-pair region (positions -290 to -240 relative to the major transcription start site). These include one upstream of the κB site and one similar to the c-fos serum response element (SRE), which is downstream of the κB site. Mutation of the κB site decreases IL-2Rα promoter activity in MT-2 cells (a T-cell line that has been transformed with human T-cell lymphotropic virus type I), but not in Jurkat cells (a T-cell leukemia line) that have been activated by phorbol 12-myristate 13-acetate (PMA). In contrast, mutation of a region upstream of the κB site decreases activity in PMA-induced Jurkat cells but increases activity in MT-2 cells. Mutation of the SRE-like site decreases activity in both cell types but the effect in PMA-induced Jurkat is more pronounced. Thus, these distinct cis-acting elements play different physiological roles in IL-2Rα gene activation in MT-2 cells and PMA-induced Jurkat T cells. These studies provide direct evidence for a functionally significant SRE-like sequence in a gene other than c-fos and the actin genes and identify other elements that are critical for IL-2Rα gene expression.