Abstract
The ability of biological systems to convert inputs from their environment into information to guide future decisions is central to life and a matter of great importance. While we know the components of many of the signaling networks that make these decisions, our understanding of the dynamic flow of information between these parts remains far more limited. T cells are an essential white blood cell type of an adaptive immune response and can discriminate between healthy and infected cells with remarkable sensitivity. This chapter describes the use of a synthetic T-cell receptor (OptoCAR) that is optically tunable within cell conjugates, providing control over the duration, and intensity of intracellular T-cell signaling dynamics. Optical control can also provide control over signaling with high spatial precision, and the OptoCAR is likely to find application more generally when modulating T-cell function with imaging approaches.
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References
Kholodenko BN (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7:165–176
Mühlhäuser WW, Fischer A, Weber W et al (2017) Optogenetics-bringing light into the darkness of mammalian signal transduction. Biochim Biophys Acta (BBA)-Mol Cell Res 1864:280–292
Castillo-Hair SM, Baerman EA, Fujita M et al (2019) Optogenetic control of bacillus subtilis gene expression. Nat Commun 10:1–11
Suzuki T, Mioka T, Tanaka K et al (2020) An optogenetic system to control membrane phospholipid asymmetry through flippase activation in budding yeast. Sci Rep 10(1):1–14
An-adirekkun J, Stewart CJ, Geller SH et al (2020) A yeast optogenetic toolkit (yotk) for gene expression control in saccharomyces cerevisiae. Biotechnol Bioeng 117:886–893
Baaske J, Gonschorek P, Engesser R et al (2018) Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells. Sci Rep 8:1–10
Yousefi OS, Günther M, Hörner M et al (2019) Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor. eLife 8:e42475
Wend S, Wagner HJ, Müller K et al (2014) Optogenetic control of protein kinase activity in mammalian cells. ACS Synth Biol 3:280–285. https://doi.org/10.1021/sb400090s
Beyer HM, Juillot S, Herbst K et al (2015) Red light-regulated reversible nuclear localization of proteins in mammalian cells and zebrafish. ACS Synth Biol 4:951–958. https://doi.org/10.1021/acssynbio.5b00004
Bonger KM, Rakhit R, Payumo AY et al (2014) General method for regulating protein stability with light. ACS Chem Biol 9:111–115
Van Bergeijk P, Adrian M, Hoogenraad CC et al (2015) Optogenetic control of organelle transport and positioning. Nature 518:111–114
Rullan M, Benzinger D, Schmidt GW et al (2018) An optogenetic platform for real-time, single-cell interrogation of stochastic transcriptional regulation. Mol Cell 70:745–756.e6. https://doi.org/10.1016/j.molcel.2018.04.012
Zhao EM, Zhang Y, Mehl J et al (2018) Optogenetic regulation of engineered cellular metabolism for microbial chemical production. Nature 555:683–687
Nguyen NT, Huang K, Zeng H et al (2021) Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety. Nat Nanotechnol 16:1424–1434
Huang Z, Wu Y, Allen ME et al (2020) Engineering light-controllable CAR T cells for cancer immunotherapy. Sci Adv 6:eaay9209
Brownlie RJ, Zamoyska R (2013) T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol 13:257–269
Harris MJ, Fuyal M, James JR (2021) Quantifying persistence in the T-cell signaling network using an optically controllable antigen receptor. Mol Syst Biol 17:e10091
Wang H, Vilela M, Winkler A et al (2016) LOVTRAP: an optogenetic system for photoinduced protein dissociation. Nat Methods 13:755–758
James JR (2018) Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density. Sci Signal 11:eaan1088
Mognol GP, González-Avalos E, Ghosh S et al (2019) Targeting the NFAT: AP-1 transcriptional complex on DNA with a small-molecule inhibitor. Proc Natl Acad Sci 116:9959–9968
James JR, Vale RD (2012) Biophysical mechanism of T-cell receptor triggering in a reconstituted system. Nature 487:64–69
Bugaj LJ, Lim WA (2019) High-throughput multicolor optogenetics in microwell plates. Nat Protoc 14:2205–2228
Thomas OS, Hörner M, Weber W (2020) A graphical user interface to design high-throughput optogenetic experiments with the optoplate-96. Nat Protoc 15:2785–2787
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Fuyal, M., James, J.R. (2024). Controlling the Potency of T Cell Activation Using an Optically Tunable Chimeric Antigen Receptor. In: Wuelfing, C., Murphy, R.F. (eds) Imaging Cell Signaling. Methods in Molecular Biology, vol 2800. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3834-7_5
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DOI: https://doi.org/10.1007/978-1-0716-3834-7_5
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