Evidence map›Paper›PMID 33988299›Full record

ArticleMolecular systems biology2021

Quantifying persistence in the T-cell signaling network using an optically controllable antigen receptor.

Michael J Harris, Muna Fuyal, John R James

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Coupling Recombinant PhyB to Cell Culture Plates and Beads.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Article
  5. Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Antigen perception in T cells by long-term Erk and NFAT signaling dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Light-inducible T cell engagers trigger, tune, and shape the activation of primary T cells.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Michael J HarrisMolecular Immunity Unit, Department of Medicine, MRC-LMB, University of Cambridge, Cambridge, UK.ORCID 0000-0002-5770-5170
Muna FuyalDivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.ORCID 0000-0003-1345-264X
John R JamesMolecular Immunity Unit, Department of Medicine, MRC-LMB, University of Cambridge, Cambridge, UK.ORCID 0000-0003-1452-7578
University of Cambridge · GBUniversity of Warwick · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M017982/1Wellcome TrustWellcome Trust 099966/Z/12/ZWellcome Trust 102195/Z/13/Z
6 · The paper itself

Abstract

T cells discriminate between healthy and infected cells with remarkable sensitivity when mounting an immune response, which is hypothesized to depend on T cells combining stimuli from multiple antigen-presenting cell interactions into a more potent response. To quantify the capacity for T cells to accomplish this, we have developed an antigen receptor that is optically tunable within cell conjugates, providing control over the duration, and intensity of intracellular T-cell signaling. We observe limited persistence within the T-cell intracellular network on disruption of receptor input, with signals dissipating entirely in ~15 min, and directly show sustained proximal receptor signaling is required to maintain gene transcription. T cells thus primarily accumulate the outputs of gene expression rather than integrate discrete intracellular signals. Engineering optical control in a clinically relevant chimeric antigen receptor (CAR), we show that this limited signal persistence can be exploited to increase CAR-T cell activation threefold using pulsatile stimulation. Our results are likely to apply more generally to the signaling dynamics of other cellular networks.

Indexed as

CalciumCell LineHEK293 CellsHumansJurkat CellsLymphocyte ActivationOptogeneticsProtein EngineeringReceptors, Antigen, T-CellReceptors, Chimeric AntigenSignal TransductionT-LymphocytesCalciumReceptors, Antigen, T-CellReceptors, Chimeric Antigencell signalingoptogeneticsreceptorsT cellstranscription factors

Identifiers

PMID33988299
PMCPMC8120804
OpenAlexW3162673581

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.