ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Distinctive CD3 heterodimeric ectodomain topologies maximize antigen-triggered activation of alpha beta T cell receptors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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
29 citing papers in PubMed, 42 citations in OpenAlex.
- Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.Immunological reviews · 2025Review
- Genomic characterization of the T-cell receptor loci inFrontiers in immunology · 2025Article
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Non-Antigenic Modulation of Antigen Receptor (TCR) Cβ-FG Loop Modulates Signalling: Implications of External Factors Influencing T-Cell Responses.International journal of molecular sciences · 2023Article
- Article
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Article
- Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Structural understanding of T cell receptor triggering.Cellular & molecular immunology · 2020Review
- DNA methylation patterns in T lymphocytes are generally stable in human pregnancies but CD3 methylation is associated with perinatal psychiatric symptoms.Brain, behavior, & immunity - health · 2020Article
- Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4Scientific reports · 2018Article
- Structural Model of the Extracellular Assembly of the TCR-CD3 Complex.Cell reports · 2016Article
- Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse.Frontiers in immunology · 2016Review
- Co-potentiation of antigen recognition: A mechanism to boost weak T cell responses and provide immunotherapy in vivo.Science advances · 2015Article
- Force-dependent transition in the T-cell receptor β-subunit allosterically regulates peptide discrimination and pMHC bond lifetime.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Structural Features of the αβTCR Mechanotransduction Apparatus That Promote pMHC Discrimination.Frontiers in immunology · 2015Review
- Molecular architecture of the αβ T cell receptor-CD3 complex.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Insights into the initiation of TCR signaling.Nature immunology · 2014Review
- The immunology connection--my first T cell receptor structure projects.Protein & cell · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The alphabeta TCR has recently been suggested to function as an anisotropic mechanosensor during immune surveillance, converting mechanical energy into a biochemical signal upon specific peptide/MHC ligation of the alphabeta clonotype. The heterodimeric CD3epsilongamma and CD3epsilondelta subunits, each composed of two Ig-like ectodomains, form unique side-to-side hydrophobic interfaces involving their paired G-strands, rigid connectors to their respective transmembrane segments. Those dimers are laterally disposed relative to the alphabeta heterodimer within the TCR complex. In this paper, using structure-guided mutational analysis, we investigate the functional consequences of a striking asymmetry in CD3gamma and CD3delta G-strand geometries impacting ectodomain shape. The uniquely kinked conformation of the CD3gamma G-strand is crucial for maximizing Ag-triggered TCR activation and surface TCR assembly/expression, offering a geometry to accommodate juxtaposition of CD3gamma and TCR beta ectodomains and foster quaternary change that cannot be replaced by the isologous CD3delta subunit's extracellular region. TCRbeta and CD3 subunit protein sequence analyses among Gnathostomata species show that the Cbeta FG loop and CD3gamma subunit coevolved, consistent with this notion. Furthermore, restoration of T cell activation and development in CD3gamma(-/-) mouse T lineage cells by interspecies replacement can be rationalized from structural insights on the topology of chimeric mouse/human CD3epsilondelta dimers. Most importantly, our findings imply that CD3gamma and CD3delta evolved from a common precursor gene to optimize peptide/MHC-triggered alphabeta TCR 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.