ArticleNature communications2024
LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation.The Journal of clinical investigation · 2026Article
- Targeting CD28 on T lineage malignancies with chimeric antigen receptor T cells.Nature communications · 2026Article
- Spatial co-expression and cell-cell communication inference from spatially resolved transcriptomics with CONCISE.bioRxiv : the preprint server for biology · 2026Article
- Oncolytic virus M1 reinvigorates CD8Cellular & molecular immunology · 2026Article
- Human LFA-1 governs T cell immune surveillance of the skin.Science immunology · 2026Article
- Jurkat T-Cell Antigen-Independent Elimination of PMA-Activated Neuroblastoma Cells Is Triggered by CCL2/CCR2, Depends Upon Lipid Raft LFA1/ICAM1 Immune Synapses, Is Mediated by m-TRAIL and Is Augmented by the TrkAIII Oncoprotein.International journal of molecular sciences · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- Three-dimensional traction technology and its application in mechanomedicine.Mechanobiology in medicine · 2025Review
- Impact of a sudden drop in ambient temperature on some phenotypic and functional properties of the camel's immune system.Journal of advanced veterinary and animal research · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tumor cells escape immunosurveillance by hampering LFA-1.Frontiers in immunology · 2025Review
- Integrin alpha L: structure, cellular functions, and emerging role in human diseases.Frontiers in immunology · 2025Review
- SubvertingBiology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 3 countries.
Funding
Abstract
T-cell cytotoxic function relies on the cooperation between the highly specific but poorly adhesive T-cell receptor (TCR) and the integrin LFA-1. How LFA-1-mediated adhesion may scale with TCR stimulation strength is ill-defined. Here, we show that LFA-1 conformation activation scales with TCR stimulation to calibrate human T-cell cytotoxicity. Super-resolution microscopy analysis reveals that >1000 LFA-1 nanoclusters provide a discretized platform at the immunological synapse to translate TCR engagement and density of the LFA-1 ligand ICAM-1 into graded adhesion. Indeed, the number of high-affinity conformation LFA-1 nanoclusters increases as a function of TCR triggering strength. Blockade of LFA-1 conformational activation impairs adhesion to target cells and killing. However, it occurs at a lower TCR stimulation threshold than lytic granule exocytosis implying that it licenses, rather than directly controls, the killing decision. We conclude that the organization of LFA-1 into nanoclusters provides a calibrated system to adjust T-cell killing to the antigen stimulation strength.
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Registered trials
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.