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Updated: Aug 5, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
16:10

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins

Published on: March 22, 2012

CD4 raft association and signaling regulate molecular clustering at the immunological synapse site

Fran Balamuth1, Jennifer L Brogdon, Kim Bottomly

  • 1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 2004
PubMed

Insights

The CD4 coreceptor regulates T cell activation by controlling the clustering of signaling molecules at the immune synapse. Palmitoylation of CD4 is crucial for this process, impacting T cell receptor and protein kinase C theta organization.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell activation involves the formation of an immunological synapse, a specialized structure for cell-cell communication.
  • The CD4 coreceptor plays a critical role in T cell signaling and activation.

Purpose of the Study:

  • To investigate the novel function of the CD4 coreceptor in regulating molecular clustering at the immunological synapse.
  • To determine the role of CD4 posttranslational modifications, specifically palmitoylation, in immune synapse organization.

Main Methods:

  • Utilized transgenic mouse models to study CD4 function.
  • Employed retroviral reconstitution studies for gene expression analysis.
  • Investigated the association of CD4 with lipid rafts and its role in T cell receptor (TCR) and protein kinase C (PKC) theta clustering.

Main Results:

  • Demonstrated that CD4 is essential for the clustering of TCR and PKC theta at the immunological synapse.
  • Showed that CD4 palmitoylation sequences are required for TCR/PKC theta raft association and subsequent clustering.
  • Identified that while raft localization is necessary, CD4 cytoplasmic tail signaling is also required for effective TCR/PKC theta clustering.

Conclusions:

  • CD4 coreceptor function is regulated by both its signaling capacity and posttranslational lipid modifications.
  • CD4 localization within lipid rafts, mediated by palmitoylation, is critical for organizing the immune synapse.
  • These findings reveal a dual mechanism controlling CD4's role in immune synapse formation and T cell activation.

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