Sustained and Dynamic Inositol Lipid Metabolism Inside and Outside the Immunological Synapse

Nat Immunol. 2002 Nov;3(11):1082-9. doi: 10.1038/ni848. Epub 2002 Oct 21.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Antigens, Viral / immunology
  • Cell Division
  • Cell Polarity
  • Chromones / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter
  • Green Fluorescent Proteins
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Humans
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology*
  • Membrane Lipids / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / physiology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / ultrastructure
  • Vanadates / pharmacology

Substances

  • Antigens, Viral
  • Chromones
  • Enzyme Inhibitors
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Luminescent Proteins
  • Membrane Lipids
  • Morpholines
  • Phosphatidylinositol Phosphates
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • pervanadate
  • phosphatidylinositol 3,4,5-triphosphate
  • Green Fluorescent Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Vanadates
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt