Evidence map›Paper›PMID 22384241›Full record

ArticlePloS one2012

Ligand mobility modulates immunological synapse formation and T cell activation.

Chih-Jung Hsu, Wan-Ting Hsieh, Abraham Waldman, Fiona Clarke, Eric S Huseby, Janis K Burkhardt, Tobias Baumgart

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 77 citations in OpenAlex.

  1. Review
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  3. Review
  4. Review
  5. Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025
    Review
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  7. Review
  8. Article
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  12. Article
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  15. Review
  16. Article
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  19. Mechanosurveillance: Tiptoeing T Cells.Frontiers in immunology · 2022
    Review
  20. 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

7 authors at 3 institutions in 1 country.

Chih-Jung HsuDepartment of Chemistry, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Wan-Ting Hsieh
Abraham Waldman
Fiona Clarke
Eric S Huseby
Janis K Burkhardt
Tobias Baumgart
University of Pennsylvania · USChildren's Hospital of Philadelphia · USUniversity of Massachusetts Chan Medical School · US

Funding

Membrane shape transition control in cellular membrane trafficking phenomenaR01GM097552 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BAUMGART, TOBIAS · 2011 to 2023
$4.5M
Cytoskeletal Remodeling During T Cell ActivationR01AI065644 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BURKHARDT, JANIS K. · 2007 to 2011
$2.0M
Biophysics of fluid lipid/protein membrane domains and immune cell signalingR21AI073409 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BAUMGART, TOBIAS · 2008 to 2009
$401k
NIAID NIH HHS R01 AI065644NIAID NIH HHS R01AI065644NIAID NIH HHS R21 AI073409NIAID NIH HHS R21AI073409NIGMS NIH HHS R01 GM097552NIGMS NIH HHS R01GM097552
6 · The paper itself

Abstract

T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+) were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

Indexed as

LigandsLymphocyte ActivationAdaptor Proteins, Signal TransducingAnimalsCalciumCluster AnalysisHumansImmunological SynapsesJurkat CellsLipid BilayersLipidsMiceMice, Inbred C57BLMicroscopy, Atomic ForcePhosphoproteinsProteinsAdaptor Proteins, Signal TransducingCalciumLigandsLipid BilayersLipidsPhosphoproteinsProteinsSLP-76 signal Transducing adaptor proteinsTyrosineZAP70 protein, humanZAP-70 Protein-Tyrosine Kinase

Identifiers

PMID22384241
PMCPMC3284572
OpenAlexW2024863574

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.