ArticleProceedings of the National Academy of Sciences of the United States of America2014
Molecular architecture of the αβ T cell receptor-CD3 complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 123 citations in OpenAlex.
- Cancer Immunotherapy: Therapeutic Limitations and Next-Generation Precision Strategies.Immune network · 2026Review
- Discriminating Post-Transplant Rejection from Infection by Detecting TCR-CD3 Oligomerization on Extracellular Vesicles Using a Ratiometric Caliper Probe.Journal of the American Chemical Society · 2026Article
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- CD28-deficient mice are vulnerable to mouse papillomavirus MmuPV1 infection of the skin and mucosae.PLoS pathogens · 2026Article
- Engineered CAR-NKT Extracellular Vesicles Suppress Tumor Progression and Enhance Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- Analyzing Point Accumulation in Nanoscale Topography (PAINT) Data to Decipher T Cell Receptor Cluster Signalling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.Haematologica · 2024Article
- TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation.Science advances · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Article
- Mini-TCRs: Truncated T cell receptors to generate T cells from induced pluripotent stem cells.Molecular therapy. Methods & clinical development · 2023Article
- Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.Biomarker research · 2023Review
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.Nature communications · 2023Article
- Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy.Frontiers in immunology · 2023Review
- Autologous, allogeneic hematopoietic cell transplantation and CAR-T/NK therapy: what is their real importance in PTCL?Frontiers in oncology · 2023Review
- Selection of High-Affinity Heterodimeric Antigen-Binding Fc Fragments from a Large Yeast Display Library.Methods in molecular biology (Clifton, N.J.) · 2023Article
24 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 3 countries.
Funding
Abstract
αβ T-cell receptor (TCR) activation plays a crucial role for T-cell function. However, the TCR itself does not possess signaling domains. Instead, the TCR is noncovalently coupled to a conserved multisubunit signaling apparatus, the CD3 complex, that comprises the CD3εγ, CD3εδ, and CD3ζζ dimers. How antigen ligation by the TCR triggers CD3 activation and what structural role the CD3 extracellular domains (ECDs) play in the assembled TCR-CD3 complex remain unclear. Here, we use two complementary structural approaches to gain insight into the overall organization of the TCR-CD3 complex. Small-angle X-ray scattering of the soluble TCR-CD3εδ complex reveals the CD3εδ ECDs to sit underneath the TCR α-chain. The observed arrangement is consistent with EM images of the entire TCR-CD3 integral membrane complex, in which the CD3εδ and CD3εγ subunits were situated underneath the TCR α-chain and TCR β-chain, respectively. Interestingly, the TCR-CD3 transmembrane complex bound to peptide-MHC is a dimer in which two TCRs project outward from a central core composed of the CD3 ECDs and the TCR and CD3 transmembrane domains. This arrangement suggests a potential ligand-dependent dimerization mechanism for TCR signaling. Collectively, our data advance our understanding of the molecular organization of the TCR-CD3 complex, and provides a conceptual framework for the TCR activation mechanism.
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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.