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Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse
Patrick S Costello1, Maighread Gallagher, Doreen A Cantrell
1Lymphocyte Activation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Abstract:
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 (PIP3) was dynamically sustained for hours as T cells responded to antigen. In addition, sustained elevation of PIP3 was essential for T cell proliferation. There was PIP3 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.