Identification of distinct populations of PI-3 kinase activity following T-cell activation.

Activation of mature CD4+ T lymphocytes by antigen-presenting cells involves engagement of the CD3/T-cell antigen receptor complex along with the CD4 surface glycoprotein and the phosphorylation of cellular proteins on tyrosine residues leading to stimulation of a variety of cellular second-messenger systems. Several recent studies have implicated non-receptor protein tyrosine kinase of the src family, especially p56lck and p59fyn, in mediating at least a portion of these tyrosine phosphorylation events. In the present study we have examined the involvement of one type of second-messenger system, phosphatidylinositol-3 kinase (PI-3 kinase), in signal transduction during antibody-induced activation of normal resting human CD4+ T cells. We demonstrate that PI-3 kinase activity is increased following co-approximation of CD4 with the T-cell receptor and that PI-3 kinase activity co-precipitates with the CD4-p56lck complex. We also show that following T-cell activation a complex containing PI-3 kinase activity can be demonstrated in CD3 epsilon immunoprecipitates which is distinct from that which interacts with p56lck.