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Qualitative and Quantitative Analysis of the Immune Synapse in the Human System Using Imaging Flow Cytometry
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The human natural killer cell immune synapse

D M Davis1, I Chiu, M Fassett

  • 1Department of Molecular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 28, 1999
PubMed

Insights

Natural killer (NK) cells form inhibitory immune synapses with target cells by clustering HLA-C molecules. This process, crucial for immunosurveillance, requires metal cations but not ATP or intact cytoskeleton.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity, surveying target cells through inhibitory receptors.
  • Inhibitory killer Ig-like receptors (KIR) interact with HLA-C molecules on target cells, mediating NK cell inhibition.
  • Understanding the formation and dynamics of these inhibitory immune synapses is key to NK cell function.

Purpose of the Study:

  • To investigate the molecular mechanisms and structural organization of inhibitory immune synapses formed between human NK cells and target cells.
  • To elucidate the role of specific molecules and cellular processes in the formation and stability of these synapses.

Main Methods:

  • Microscopy techniques to visualize protein distribution at the immune synapse.
  • Functional assays involving metal cations, ATP depletion, and cytoskeletal inhibitors.
  • Analysis of protein clustering and movement at the target/NK cell interface.

Main Results:

  • Inhibitory KIR induced HLA-C clustering at the target cell surface, forming stable inhibitory immune synapses.
  • Protein organization at the synapse showed HLA-C/KIR in rings around ICAM-1/LFA-1, distinct from T cell synapses.
  • Synapse formation required divalent metal cations but was independent of ATP and cytoskeletal integrity.

Conclusions:

  • Supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.
  • The distinct organization of inhibitory synapses highlights unique NK cell recognition mechanisms.
  • Divalent metal cations are essential for KIR-mediated synapse formation, explaining the effect of metal chelators.

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