OptoREACT: Optogenetic Receptor Activation on Nonengineered Human T Cells.

Autor: Armbruster A; INM - Leibniz Institute for New Materials, Campus D2 2, Saarbrücken 66123, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany., Ehret AK; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19A, Freiburg 79104, Germany., Russ M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany., Idstein V; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19A, Freiburg 79104, Germany., Klenzendorf M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany., Gaspar D; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany., Juraske C; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19A, Freiburg 79104, Germany., Yousefi OS; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany., Schamel WW; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Centre Freiburg, and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, Freiburg 79106, Germany., Weber W; INM - Leibniz Institute for New Materials, Campus D2 2, Saarbrücken 66123, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.; Department of Materials Science and Engineering, Saarland University, Campus D2 2, Saarbrücken 66123, Germany., Hörner M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, Freiburg 79104, Germany.; Faculty of Biology, University of Freiburg, Schänzlestr. 1, Freiburg 79104, Germany.
Jazyk: angličtina
Zdroj: ACS synthetic biology [ACS Synth Biol] 2024 Mar 15; Vol. 13 (3), pp. 752-762. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1021/acssynbio.3c00518
Abstrakt: 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 ( Opto genetic Re ceptor Act ivation) 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.
Databáze: MEDLINE