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 (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.
Costello
Patrick S
PS
Lymphocyte Activation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Gallagher
Maighread
M
Cantrell
Doreen A
DA
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000956:Antigens, Viral / Q000276:immunology; D002455:Cell Division; D016764:Cell Polarity; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D014638:Vanadates / Q000494:pharmacology
D000956:Antigens, Viral; D002867:Chromones; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008164:Luminescent Proteins; D008563:Membrane Lipids; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014638:Vanadates; C076715:pervanadate; C060974:phosphatidylinositol 3,4,5-triphosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one