Integrin-Dependent Organization and Bidirectional Vesicular Traffic at Cytotoxic Immune Synapses

Dongfang Liu, Yenan T. Bryceson, Tobias Meckel, Gaia Vasiliver-Shamis, Michael L. Dustin, Eric O. Long

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To understand the dynamics and control of cytotoxic immune synapses, we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the β2 integrin ligand ICAM-1. Ligands of coactivation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalImmunity
Volume31
Issue number1
DOIs
StatePublished - Jul 17 2009

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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