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Continuous T cell receptor signaling required for synapse maintenance and full effector potential
Johannes B Huppa1, Michael Gleimer, Cenk Sumen
1Stanford University School of Medicine, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, Beckman Center B221, 279 Campus Drive, Stanford, California 94305, USA.
Nature Immunology
|July 15, 2003
Summary
T cell receptor (TCR) signaling persists for hours during prolonged cell contact, demonstrating a cumulative effect essential for maintaining the immunological synapse and driving T helper cell activation and proliferation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- T cell receptor (TCR) signaling initiates T helper cell activation.
- The role of sustained TCR signaling during prolonged cell-cell contact remains unclear.
Purpose of the Study:
- To investigate the duration and function of TCR signaling during sustained T cell-antigen-presenting cell interactions.
- To determine the necessity of persistent TCR signaling for immunological synapse stability and T cell function.
Main Methods:
- Simultaneous tracking of TCR-CD3 complex and phosphoinositide 3-kinase (PI3K) activity in single T cells.
- Utilized three-dimensional video microscopy for real-time observation.
- Investigated the effects of blocking cell-cell interactions on signaling and cellular responses.
Main Results:
- TCR-dependent signaling persisted for up to 10 hours, despite rapid TCR-CD3 internalization.
- Blocking T cell-antigen-presenting cell interactions led to synapse dissolution.
- Reduced interleukin 2 production and cellular proliferation were observed upon blocking the interaction.
Conclusions:
- TCR signaling has a prolonged, cumulative effect crucial for immunological synapse maintenance.
- Sustained TCR signaling is necessary for T helper cell activation, interleukin 2 production, and proliferation.