ArticleThe Journal of experimental medicine2012
Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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.
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Who cites it
64 citing papers in PubMed, 111 citations in OpenAlex.
- Close Contacts Unlocked: Nanopore-Stabilized Microvilli Bypass T Cell Receptor-Ligand-Dependent T Cell Activation.ACS nano · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Targeting the N-acetyltransferase 10/DKK2 axis enhances CD8+ T cell antitumor activity in colorectal cancer models.The Journal of clinical investigation · 2026Article
- CD4/CD8-p56Biomolecules · 2025Review
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- NPC1L1 on pancreatic adenocarcinoma cell functions as a two-pronged checkpoint against antitumor activity.Innovation (Cambridge (Mass.)) · 2025Article
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.Communications biology · 2023Article
- Self-programmed dynamics of T cell receptor condensation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles.Nature communications · 2022Article
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Cancer metabolism and tumor microenvironment: fostering each other?Science China. Life sciences · 2022Review
- Article
- PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain.Nature communications · 2021Article
- Review
- Intrinsic Disorder in the T Cell Receptor Creates Cooperativity and Controls ZAP70 Binding.Biophysical journal · 2021Article
- Peptide-MHC Binding Reveals Conserved Allosteric Sites in MHC Class I- and Class II-Restricted T Cell Receptors (TCRs).Journal of molecular biology · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.
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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.