Evidence map›Paper›PMID 25666810›Full record

ArticleThe Journal of cell biology2015

F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse.

William A Comrie, Alexander Babich, Janis K Burkhardt

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
12.5field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 164 citations in OpenAlex.

  1. Review
  2. Alterations of actin in aging.Journal of cell science · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025
    Review
  9. Cancer cells suppress NK cell activity by actin-driven polarization of inhibitory ligands to the immunological synapse.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

50 more citing papers are in PubMed but not listed here.

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.

William A ComrieDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Alexander BabichDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Janis K BurkhardtDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 jburkhar@mail.med.upenn.edu.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
TRAINING PROGRAM/RHEUMATIC DISEASEST32AR007442 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BEHRENS, EDWARD M, MERKEL, PETER A · 1986 to 2018
$5.8M
Cytoskeletal Remodeling During T Cell ActivationR01AI065644 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BURKHARDT, JANIS K. · 2007 to 2011
$2.0M
Costimulatory ligand mobility effects on T cell activationR01GM104867 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI BURKHARDT, JANIS K. · 2013 to 2016
$1.3M
NCI NIH HHS P30 CA016520NIAID NIH HHS R01 AI065644NIAID NIH HHS R01AI065644NIAMS NIH HHS 5T32AR7442NIAMS NIH HHS T32 AR007442NIGMS NIH HHS GM104867NIGMS NIH HHS R01 GM104867
6 · The paper itself

Abstract

Integrin-dependent interactions between T cells and antigen-presenting cells are vital for proper T cell activation, effector function, and memory. Regulation of integrin function occurs via conformational change, which modulates ligand affinity, and receptor clustering, which modulates valency. Here, we show that conformational intermediates of leukocyte functional antigen 1 (LFA-1) form a concentric array at the immunological synapse. Using an inhibitor cocktail to arrest F-actin dynamics, we show that organization of this array depends on F-actin flow and ligand mobility. Furthermore, F-actin flow is critical for maintaining the high affinity conformation of LFA-1, for increasing valency by recruiting LFA-1 to the immunological synapse, and ultimately for promoting intracellular cell adhesion molecule 1 (ICAM-1) binding. Finally, we show that F-actin forces are opposed by immobilized ICAM-1, which triggers LFA-1 activation through a combination of induced fit and tension-based mechanisms. Our data provide direct support for a model in which the T cell actin network generates mechanical forces that regulate LFA-1 activity at the immunological synapse.

Indexed as

ActinsB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell CommunicationCells, CulturedEnzyme ActivationHumansImmunological SynapsesIntegrin beta1Intercellular Adhesion Molecule-1Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Myosin Type IIProtein BindingProtein Structure, TertiaryActinsIntegrin beta1Intercellular Adhesion Molecule-1Lymphocyte Function-Associated Antigen-1Myosin Type II

Identifiers

PMID25666810
PMCPMC4332248
OpenAlexW1976044471

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.