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Qualitative and Quantitative Analysis of the Immune Synapse in the Human System Using Imaging Flow Cytometry
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Regulated movement of CD4 in and out of the immunological synapse

Henry Kao1, Joseph Lin, Dan R Littman

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 4, 2008
PubMed

Insights

Preventing CD4 phosphorylation at S408 blocked its removal from the immunological synapse (IS), not its recruitment. This prolonged CD4 accumulation did not affect T cell activation, highlighting PKCtheta

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The transient accumulation of CD4 at the immunological synapse (IS) and its role in T cell activation remain unclear.
  • Understanding the dynamics of CD4 at the IS is crucial for deciphering T cell signaling pathways.

Purpose of the Study:

  • To investigate the mechanism and significance of CD4 transient accumulation at the IS.
  • To determine the role of CD4 phosphorylation at serine 408 (S408) in its IS dynamics and T cell activation.

Main Methods:

  • Site-directed mutagenesis of a serine phosphorylation site (S408) in the cytoplasmic tail of murine CD4.
  • Analysis of CD4 recruitment and removal dynamics at the IS using microscopy.
  • Assessment of T cell activation, cytokine production, and proliferation in wild-type and PKCtheta-deficient T cells.

Main Results:

  • Mutation of S408 prevented CD4 removal from the IS, but not its initial recruitment.
  • Prolonged CD4 accumulation at the IS did not impact T cell activation, cytokine production, or proliferation.
  • T cells deficient in Protein Kinase C theta (PKCtheta) showed enhanced and prolonged CD4 accumulation at the IS.

Conclusions:

  • PKCtheta is the critical Protein Kinase C isoform responsible for regulating CD4 movement out of the IS.
  • A model is proposed where PKCtheta phosphorylates CD4 at the IS, facilitating its subsequent removal.
  • PKCtheta's role in T cell activation involves IS recruitment and phosphorylation of substrates to maintain IS protein turnover dynamism.

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