ArticleProceedings of the National Academy of Sciences of the United States of America2016
Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 239 citations in OpenAlex.
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- The geometry of pMHC-coated nanoparticles and T-cell receptor clusters governs the sensitivity-specificity trade-off in T-cell response: a modeling investigation.Immunology and cell biology · 2026Article
- A comparative mathematical modeling study of phenotypic approaches to T cell activation.Scientific reports · 2025Article
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- Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4European journal of immunology · 2025Article
- Step-Wise Assembly of LAT Signaling Clusters Immediately After T Cell Receptor Triggering Contributes to Signal Propagation.International journal of molecular sciences · 2025Article
- Cell-Membrane-Anchored DNA Nanoplatform for Programming Cellular Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Analyzing Point Accumulation in Nanoscale Topography (PAINT) Data to Decipher T Cell Receptor Cluster Signalling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Frontiers in mechanobiology and mechanomedicine.Med-X · 2025Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR-CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR-CD3 complexes. We found that only TCR-CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR-pMHC affinity determined the density of TCR-CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR-CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination.
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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.