The human interleukin-2 (IL-2) receptor (IL2R) is being studied in order to understand specific critical components of the T cell immune response in normal and neoplastic cells. The approaches used are based on (1) biochemical analysis of high, intermediate, and low affinity IL2Rs; (2) characterization of transcription regulatory sequences in the IL2R-alpha gene; (3) characterization of DNA binding proteins for regulatory regions. We were the first to identify the existence of a 65 to 77 kD glycoprotein (p70, IL2R- beta) which is a component of the high affinity human IL2R, distinct from IL2R-alpha (p55, Tac antigen), and which can bind IL- 2. IL2R-beta mediates the generation of LAK cells and IL-2 induced augmentation of NK activity. Further it is present on resting CD4 and CD8 positive T cells, and can be induced on B cells and monocytes. We have partially mapped the region of the IL2R-alpha gene necessary for transcriptional activity using IL2R-alpha-CAT constructs in transfection experiments. We previously found evidence for: (1) a requirement for a larger promoter region in Jurkat cells than in HTLV-l transformed T cells; (2) the ability to convert the Jurkat pattern to the HTLV-l pattern by cotransfection with tat-l; (3) a region that functions as a negative regulatory region in HTLV-l transformed T cell lines. We now have characterized regions of DNA that bind proteins in vitro. One of these is 3' to the transcription initiation site; the others are 5' to it. One of the 5' sites is PMA inducible in Jurkat and can bind the nuclear factor, NF-kB, which binds to the kappa immunoglobulin gene enhancer. The regulation of expression of the IL2R-alpha gene appears to depend on both positive and negative regulatory elements. We have also identified a new gene, Act-2, which is induced in T cells within 15 min of exposure to PHA, reaching maximal levels of mRNA expression in 4 h and declining significantly by 16 h. This gene encodes a secreted product and has been expressed using a baculovirus vector. Efforts to study its biologic function and molecular regulation are in progress.
