ArticleThe Journal of biological chemistry2012
Cholesterol and sphingomyelin drive ligand-independent T-cell antigen receptor nanoclustering.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 176 citations in OpenAlex.
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- Close Contacts Unlocked: Nanopore-Stabilized Microvilli Bypass T Cell Receptor-Ligand-Dependent T Cell Activation.ACS nano · 2026Article
- CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.MedScience · 2026Article
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Allostery in Biomolecular Condensates.Journal of molecular biology · 2026Review
- Targeting necrotic lipid release in tumors enhances immunosurveillance and cancer immunotherapy of glioblastoma.Cell research · 2025Article
- Advances in integrating biomaterials with CAR-T cells for enhancing solid tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- T cell cholesterol transport links intestinal immune responses to dietary lipid absorption.Science (New York, N.Y.) · 2025Article
- Article
- Epidermal and Dermal T Cells Exhibit Distinct Proteomic Signatures.International journal of molecular sciences · 2025Article
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia.Cellular & molecular immunology · 2025Article
- 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
- Disrupting cholesterol homeostasis in T cells boosts antitumour responses.Nature metabolism · 2025Article
- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The T-cell antigen receptor (TCR) exists in monomeric and nanoclustered forms independently of antigen binding. Although the clustering is involved in the regulation of T-cell sensitivity, it is unknown how the TCR nanoclusters form. We show that cholesterol is required for TCR nanoclustering in T cells and that this clustering enhances the avidity but not the affinity of the TCR-antigen interaction. Investigating the mechanism of the nanoclustering, we found that radioactive photocholesterol specifically binds to the TCRβ chain in vivo. In order to reduce the complexity of cellular membranes, we used a synthetic biology approach and reconstituted the TCR in liposomes of defined lipid composition. Both cholesterol and sphingomyelin were required for the formation of TCR dimers in phosphatidylcholine-containing large unilamellar vesicles. Further, the TCR was localized in the liquid disordered phase in giant unilamellar vesicles. We propose a model in which cholesterol and sphingomyelin binding to the TCRβ chain causes TCR dimerization. The lipid-induced TCR nanoclustering enhances the avidity to antigen and thus might be involved in enhanced sensitivity of memory compared with naive T cells. Our work contributes to the understanding of the function of specific nonannular lipid-membrane protein interactions.
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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.