ReviewThe Journal of biological chemistry2020
The structural basis of T-cell receptor (TCR) activation: An enduring enigma.
Review in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
113 citing papers in PubMed, 111 citations in OpenAlex.
- Machine Learning for TCR Repertoire Epitope Annotation and Pattern Discovery.Immunological reviews · 2026Review
- Subtractive Proteomics and Immunoinformatics-Guided Design of a Multi-Epitope Vaccine Against Aspergillus fumigatus.Probiotics and antimicrobial proteins · 2026Article
- From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.Antibody therapeutics · 2026Review
- Computational prediction of TCR cross-reactivity: principles, challenges and translational opportunities.Journal of translational medicine · 2026Review
- Mapping the TCR landscape: computational tools empowering translational immunology and therapy design.Journal for immunotherapy of cancer · 2026Review
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- A Novel Pathogenic Variant in TRAC Gene Associated with SCID Phenotype: Expanding the Genetic and Clinical Spectrum.Journal of clinical immunology · 2026Article
- Three-dimensional multimodal imaging for predicting early recurrence of hepatocellular carcinoma after surgical resection.Journal of advanced research · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Phosphorylation shapes antigen presentation and immune recognition: mechanistic insights and translational perspectives.Frontiers in immunology · 2026Review
- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Preparation of ESAT6-Fc Fusion Protein and Its Therapeutic Efficacy and Immune Mechanisms in Allergic Asthma Mice via Intranasal Immunization.Molecules (Basel, Switzerland) · 2025Article
- Hydrophobic complementarity-determining region 3 (CDR3) sequences elucidate the cardiotoxic effects of immune checkpoint inhibitors.Research square · 2025Article
- The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.Nature communications · 2025Article
- Disrupting explicit encoding paradigms: property-interactive transformers decode T-cell receptor specificity beyond dataset biases.Briefings in bioinformatics · 2025Article
- A kinetic gatekeeper: TCR-pMHC dissociation dynamics determine T cell activation efficacy.Protein science : a publication of the Protein Society · 2025Article
- Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors.Biomedicines · 2025Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
T cells are critical for protective immune responses to pathogens and tumors. The T-cell receptor (TCR)-CD3 complex is composed of a diverse αβ TCR heterodimer noncovalently associated with the invariant CD3 dimers CD3ϵγ, CD3ϵδ, and CD3ζζ. The TCR mediates recognition of antigenic peptides bound to MHC molecules (pMHC), whereas the CD3 molecules transduce activation signals to the T cell. Whereas much is known about downstream T-cell signaling pathways, the mechanism whereby TCR engagement by pMHC is first communicated to the CD3 signaling apparatus, a process termed early T-cell activation, remains largely a mystery. In this review, we examine the molecular basis for TCR activation in light of the recently determined cryoEM structure of a complete TCR-CD3 complex. This structure provides an unprecedented opportunity to assess various signaling models that have been proposed for the TCR. We review evidence from single-molecule and structural studies for force-induced conformational changes in the TCR-CD3 complex, for dynamically-driven TCR allostery, and for pMHC-induced structural changes in the transmembrane and cytoplasmic regions of CD3 subunits. We identify major knowledge gaps that must be filled in order to arrive at a comprehensive model of TCR activation that explains, at the molecular level, how pMHC-specific information is transmitted across the T-cell membrane to initiate intracellular signaling. An in-depth understanding of this process will accelerate the rational design of immunotherapeutic agents targeting the TCR-CD3 complex.
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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.