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Updated: Aug 9, 2026
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
Complex and dynamic redistribution of NF-kappaB signaling intermediates in response to T cell receptor stimulation
Brian C Schaefer1, John W Kappler, Abraham Kupfer
1Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. bschaefer@usuhs.mil
Insights
T-cell receptor (TCR) activation involves complex protein movement. PKC and Bcl10 relocate dynamically to the central supramolecular activation cluster (c-SMAC) during T-cell signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- The central supramolecular activation cluster (c-SMAC) is crucial for T cell activation.
- T-cell receptor (TCR) signaling pathways regulate immune responses.
- NF-kappaB activation is a key downstream event in T cell signaling.
Purpose of the Study:
- To investigate the dynamic relocalization of signaling intermediates during TCR activation.
- To elucidate the movement of PKC and Bcl10 within the T cell/APC junction.
- To understand the spatial and temporal regulation of NF-kappaB pathway components.
Main Methods:
- Utilized advanced microscopy techniques to visualize protein dynamics.
- Tracked the localization of protein kinase C (PKC) and Bcl10 during T cell activation.
- Analyzed protein enrichment at the supramolecular activation cluster (c-SMAC) over time.
Main Results:
- TCR activation leads to PKC enrichment at the c-SMAC.
- Bcl10 initially relocalizes to cytoplasmic structures distant from the c-SMAC.
- These Bcl10 structures subsequently migrate to and enrich at the c-SMAC.
- NF-kappaB signaling intermediates exhibit distinct, phased relocalization patterns.
Conclusions:
- TCR activation of NF-kappaB is a complex process involving dynamic protein relocalization.
- Signaling intermediates like PKC and Bcl10 undergo distinct spatial and temporal movements.
- Understanding these dynamic events is key to comprehending T cell activation and immune responses.
Abstract:
The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKC and Bcl10, two intermediates in TCR activation of NF-kappaB, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKC at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-kappaB therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.
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