Evidence map›Paper›PMID 39199389›Full record

ArticleBiomolecules2024

Advanced Quantification of Receptor-Ligand Interaction Lifetimes via Single-Molecule FRET Microscopy.

Lukas Schrangl, Vanessa Mühlgrabner, René Platzer, Florian Kellner, Josephine Wieland, Reinhard Obst, José L Toca-Herrera, Johannes B Huppa, Gerhard J Schütz, Janett Göhring

Abstract read
In one paragraph

Article in Biomolecules, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

10 authors.

Lukas SchranglInstitute of Biophysics, Department of Bionanosciences, University of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria.ORCID 0000-0002-0420-7872
Vanessa MühlgrabnerInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.ORCID 0009-0004-3331-8741
René PlatzerInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.ORCID 0009-0001-3399-4721
Florian KellnerInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.ORCID 0000-0001-5931-3798
Josephine WielandInstitute for Immunology, Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.
Reinhard ObstInstitute for Immunology, Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.ORCID 0000-0002-4839-207X
José L Toca-HerreraInstitute of Biophysics, Department of Bionanosciences, University of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria.ORCID 0000-0001-8951-2616
Johannes B HuppaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.ORCID 0000-0003-2634-8198
Gerhard J SchützInstitute of Applied Physics, TU Wien, Wiedner Hauptstr. 8-10, 1040 Vienna, Austria.ORCID 0000-0003-1542-1089
Janett GöhringInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.ORCID 0000-0002-6755-5305

Funding

Austrian Science Fund FWF P 32307FWF Austrian Science Fund P32307-BVienna Science and Technology Fund LS13-030
6 · The paper itself

Abstract

Receptor-ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR-pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR-pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor-ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model's accuracy and robustness across multiple TCR-pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

Indexed as

Fluorescence Resonance Energy TransferReceptors, Antigen, T-CellSingle Molecule ImagingHumansKineticsLigandsMajor Histocompatibility ComplexProtein BindingT-LymphocytesLigandsReceptors, Antigen, T-Cellantigen sensitivitybond lifetime quantificationreceptor-ligand interactionsimulationsingle-molecule FRETsingle-molecule microscopysurvival analysisT cell activationT cell receptor

Identifiers

PMID39199389
PMCPMC11352576

What Socratic holds

Textmetadata
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 Socratic graph.