ArticleProceedings of the National Academy of Sciences of the United States of America2021
T cells selectively filter oscillatory signals on the minutes timescale.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Improvement in model flexibility reveals signaling pathway in T cell responses to pulsatile stimuli.NPJ systems biology and applications · 2026Article
- Engineering programmable CAR and antigen pairing via drug-gated light activation.Nature communications · 2026Article
- Interrogating Physiological Functions with Light and Chemicals.Annual review of physiology · 2026Review
- Decoding the temporal dimension of innate immunity in intravesical BCG therapy.Frontiers in immunology · 2026Article
- Targeting liver metastases in uveal melanoma: ATX-LPA mediated immunosuppression and novel therapeutic approaches.Frontiers in immunology · 2026Article
- T cell decision-making decodes the dynamic antigenic landscape.Frontiers in immunology · 2026Review
- Coupling Recombinant PhyB to Cell Culture Plates and Beads.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Strategies for multimodal spatiotemporal profiling of phosphorylation in cilia biology.Journal of cell science · 2025Review
- Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Optogenetic control of T cells for immunomodulation.Essays in biochemistry · 2025Review
- Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4European journal of immunology · 2025Article
- Optogenetic Clustering and Stimulation of the T Cell Receptor in Nongenetically Modified Human T Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The current landscape of optogenetics for the enhancement of adoptive T-cell therapy.Discovery immunology · 2025Review
- Opto-CD28-REACT: optogenetic co-stimulatory receptor activation on non-engineered human T cells.Frontiers in immunology · 2025Article
- Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.International journal of molecular sciences · 2024Review
- Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells.Acta pharmaceutica Sinica. B · 2024Article
- Engineering a Programmed Death-Ligand 1-Targeting Monobody Via Directed Evolution for SynNotch-Gated Cell Therapy.ACS nano · 2024Article
- Dynamic hydrogen peroxide levels reveal a rate-dependent sensitivity in B-cell lymphoma signaling.Scientific reports · 2024Article
- Rapid Optogenetic Clustering in the Cytoplasm with BcLOVclust.Journal of molecular biology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
T cells experience complex temporal patterns of stimulus via receptor-ligand-binding interactions with surrounding cells. From these temporal patterns, T cells are able to pick out antigenic signals while establishing self-tolerance. Although features such as duration of antigen binding have been examined, our understanding of how T cells interpret signals with different frequencies or temporal stimulation patterns is relatively unexplored. We engineered T cells to respond to light as a stimulus by building an optogenetically controlled chimeric antigen receptor (optoCAR). We discovered that T cells respond to minute-scale oscillations of activation signal by stimulating optoCAR T cells with tunable pulse trains of light. Systematically scanning signal oscillation period from 1 to 150 min revealed that expression of CD69, a T cell activation marker, reached a local minimum at a period of ∼25 min (corresponding to 5 to 15 min pulse widths). A combination of inhibitors and genetic knockouts suggest that this frequency filtering mechanism lies downstream of the Erk signaling branch of the T cell response network and may involve a negative feedback loop that diminishes Erk activity. The timescale of CD69 filtering corresponds with the duration of T cell encounters with self-peptide-presenting APCs observed via intravital imaging in mice, indicating a potential functional role for temporal filtering in vivo. This study illustrates that the T cell signaling machinery is tuned to temporally filter and interpret time-variant input signals in discriminatory ways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.