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Staging and resetting T cell activation in SMACs
Benjamin A Freiberg1, Hannah Kupfer, William Maslanik
1Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA.
Nature Immunology
|September 24, 2002
Summary
T cell activation involves dynamic signaling clusters. Pre-supramolecular activation cluster (SMAC) signals promote adhesion, while in-SMAC signaling is crucial for productive T cell responses.
Area of Science:
- Immunology
- Cellular Biology
- Biochemistry
Background:
- T cell activation requires productive interaction with antigen-presenting cells (APCs).
- Receptors and associated kinases assemble into supramolecular activation clusters (SMACs) at the T cell-APC contact area.
- Understanding intracellular signaling within SMACs is key to T cell function.
Purpose of the Study:
- To investigate the spatiotemporal dynamics of intracellular signaling during T cell-APC interactions.
- To elucidate the role of SMAC formation in T cell activation.
- To differentiate signaling events preceding and following SMAC formation.
Main Methods:
- Three-dimensional immunofluorescence microscopy was employed.
- Localization of key signaling molecules including CD3, CD45, talin, phosphotyrosine, Lck, and phosphorylated ZAP-70 was analyzed.
- Analysis was performed in T cell-APC conjugates.
Main Results:
- Two distinct phases of spatial-temporal signaling activation were observed at the T cell-APC contact area.
- An initial phase of activation occurred before SMAC formation.
- A subsequent phase of activation occurred within the SMAC, separated by a transient inactivation mediated by CD45.
Conclusions:
- Pre-SMAC signaling events are sufficient to trigger cell adhesion.
- Productive T cell responses necessitate orchestrated signaling events within the SMAC.
- CD45 plays a regulatory role, causing a brief inactivation period between pre-SMAC and SMAC signaling phases.