Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse

T cell activation is triggered by several hours of contact with peptide–major histocompatibility (MHC) complexes on the surface of antigen-presenting cells (APCs). The nature and location of the sustained signal transduction pathways required for T cell activation are unknown. We show here that the production of phosphatidylinositol(3,4,5)triphosphate (PIP 3 ) was dynamically sustained for hours as T cells responded to antigen. In addition, sustained elevation of PIP 3 was essential for T cell proliferation. There was PIP 3 accumulation in the T cell–APC contact zone and at the antipodal pole of the cell. The immune synapse is thus not the sole site of sustained signal transduction in activated T cells.