Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene

Abstract

Concanavalin A (Con A), which together with phorbol myristate acetate (PMA) can activate the human T cell line Jurkat to produce interleukin 2 (IL 2), is shown to depend on the expression of the T3/T cell antigen receptor heterodimer (T3/Ti) complex to induce activation. alpha-methyl mannoside was able to reverse all of the observed effects of Con A on intracellular biochemical events. Therefore, ligand-receptor occupancy appears to be required for sustaining biochemical events associated with triggering the T3/Ti complex. Studies of the time-dependent requirements for the two stimuli required for activation revealed that simultaneous stimulation with both Con A and PMA is required for 2 to 4 hr for the cell to commit itself to activation, as measured by the appearance of secreted IL 2. This 2- to 4-hr requirement correlated precisely with the appearance of IL 2 mRNA, and the appearance of IL 2 transcripts depended on protein synthesis during this critical time period.