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Updated: Jul 4, 2025
Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
OptoREACT: Optogenetic Receptor Activation on Nonengineered Human T Cells
Anja Armbruster1,2,3, Anna K Ehret2,3,4,5, Marissa Russ2,3,4
1INM - Leibniz Institute for New Materials, Campus D2 2, Saarbrücken 66123, Germany.
Abstract:
Optogenetics is a versatile and powerful tool for the control and analysis of cellular signaling processes. The activation of cellular receptors by light using optogenetic switches usually requires genetic manipulation of cells. However, this considerably limits the application in primary, nonengineered cells, which is crucial for the study of physiological signaling processes and for controlling cell fate and function for therapeutic purposes. To overcome this limitation, we developed a system for the light-dependent extracellular activation of cell surface receptors of nonengineered cells termed OptoREACT (Optogenetic Receptor Activation) based on the light-dependent protein interaction of A. thaliana phytochrome B (PhyB) with PIF6. In the OptoREACT system, a PIF6-coupled antibody fragment binds the T cell receptor (TCR) of Jurkat or primary human T cells, which upon illumination is bound by clustered phytochrome B to induce receptor oligomerization and activation. For clustering of PhyB, we either used tetramerization by streptavidin or immobilized PhyB on the surface of cells to emulate the interaction of a T cell with an antigen-presenting cell. We anticipate that this extracellular optogenetic approach will be applicable for the light-controlled activation of further cell surface receptors in primary, nonengineered cells for versatile applications in fundamental and applied research.
Insights
Researchers developed OptoREACT, a novel optogenetic system enabling light-controlled activation of cell surface receptors in non-genetically engineered cells. This breakthrough allows for precise manipulation of cellular signaling for therapeutic and research applications.
Area of Science:
- Biotechnology
- Molecular Biology
- Cellular Signaling
Background:
- Optogenetics offers powerful control over cellular processes but typically requires genetic modification.
- This limitation restricts its use in primary cells, hindering physiological studies and therapeutic applications.
Purpose of the Study:
- To develop a non-invasive, light-inducible system for activating cell surface receptors in non-engineered cells.
- To overcome the limitations of genetic manipulation in optogenetic applications.
Main Methods:
- Developed OptoREACT (Optogenetic Receptor Activation) using light-dependent interactions between phytochrome B (PhyB) and PIF6.
- Utilized PIF6-coupled antibody fragments to target T cell receptors (TCRs) on Jurkat and primary human T cells.
- Employed streptavidin-mediated tetramerization or cell surface immobilization of PhyB to induce receptor clustering and activation upon illumination.
Main Results:
- Demonstrated successful light-dependent activation of TCRs in non-engineered T cells using the OptoREACT system.
- Showcased the ability to cluster and activate cell surface receptors extracellularly without genetic manipulation.
- Validated the system's potential by emulating T cell-antigen-presenting cell interactions.
Conclusions:
- OptoREACT provides a versatile extracellular optogenetic approach for controlling cell surface receptors in primary, non-engineered cells.
- This method expands the applicability of optogenetics in fundamental research and therapeutic development.
- The system holds promise for light-controlled activation of diverse cell surface receptors.
