ArticleProceedings of the National Academy of Sciences of the United States of America2015
The coreceptor CD4 is expressed in distinct nanoclusters and does not colocalize with T-cell receptor and active protein tyrosine kinase p56lck.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.Molecular therapy. Advances · 2026Article
- Multivalent adaptor networks generate nanoscale organisation within T cell signalling condensates.bioRxiv : the preprint server for biology · 2026Article
- Zinc-mediated dynamics of CD4/CD8α co-receptors and Lck kinase: implications for zinc homeostasis, immune response, and biotechnological innovations.Metallomics : integrated biometal science · 2025Review
- Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Article
- The ubiquitous nanocluster: A molecular scale organizing principle that governs cellular information flow.Current opinion in cell biology · 2024Review
- Crosstalking with Dendritic Cells: A Path to Engineer Advanced T Cell Immunotherapy.Frontiers in systems biology · 2024Article
- Plasma membrane topography governs the 3D dynamic localization of IgM B cell antigen receptor clusters.The EMBO journal · 2023Article
- Pre-organized landscape of T cell surface.Frontiers in immunology · 2023Review
- The kinase occupancy of T cell coreceptors reconsidered.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The interplay between membrane topology and mechanical forces in regulating T cell receptor activity.Communications biology · 2022Review
- CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells.Nature communications · 2022Article
- Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling.Science immunology · 2021Article
- CD146 bound to LCK promotes T cell receptor signaling and antitumor immune responses in mice.The Journal of clinical investigation · 2021Article
- Rapid statistical discrimination of fluorescence images of T cell receptors on immobilizing surfaces with different coating conditions.Scientific reports · 2021Article
- Challenges and Opportunities in the Statistical Analysis of Multiplex Immunofluorescence Data.Cancers · 2021Review
- Innate immune receptor clustering and its role in immune regulation.Journal of cell science · 2021Review
- Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding.Viruses · 2021Article
- Gamma Delta TCR and the WC1 Co-Receptor Interactions in Response toFrontiers in immunology · 2021Article
- Plasma Membrane Integrates Biophysical and Biochemical Regulation to Trigger Immune Receptor Functions.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
CD4 molecules on the surface of T lymphocytes greatly augment the sensitivity and activation process of these cells, but how it functions is not fully understood. Here we studied the spatial organization of CD4, and its relationship to T-cell antigen receptor (TCR) and the active form of Src kinase p56lck (Lck) using single and dual-color photoactivated localization microscopy (PALM) and direct stochastic optical reconstruction microscopy (dSTORM). In nonactivated T cells, CD4 molecules are clustered in small protein islands, as are TCR and Lck. By dual-color imaging, we find that CD4, TCR, and Lck are localized in their separate clusters with limited interactions in the interfaces between them. Upon T-cell activation, the TCR and CD4 begin clustering together, developing into microclusters, and undergo a larger scale redistribution to form supramolecluar activation clusters (SMACs). CD4 and Lck localize in the inner TCR region of the SMAC, but this redistribution of disparate cluster structures results in enhanced segregation from each other. In nonactivated cells these preclustered structures and the limited interactions between them may serve to limit spontaneous and random activation events. However, the small sizes of these island structures also ensure large interfacial surfaces for potential interactions and signal amplification when activation is initiated. In the later activation stages, the increasingly larger clusters and their segregation from each other reduce the interfacial surfaces and could have a dampening effect. These highly differentiated spatial distributions of TCR, CD4, and Lck and their changes during activation suggest that there is a more complex hierarchy than previously thought.
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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.