ArticleStructure (London, England : 1993)2016
An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry.
Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed.
- TcrDesign: de novo design of epitope-specific full-length T cell receptors.Science China. Life sciences · 2026Article
- Epitope mapping via in vitro deep mutational scanning methods and its applications.The Journal of biological chemistry · 2025Review
- Enhanced T cell receptor specificity through framework engineering.Frontiers in immunology · 2024Article
- Strategies and rules for tuning TCR-derived therapy.Expert reviews in molecular medicine · 2023Review
- SARS-CoV-2 infection establishes a stable and age-independent CD8Nature communications · 2023Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
- Engineering Proteins by Combining Deep Mutational Scanning and Yeast Display.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Engineering soluble T-cell receptors for therapy.The FEBS journal · 2021Review
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.Biochemistry · 2020Article
- Deep mutagenesis in the study of COVID-19: a technical overview for the proteomics community.Expert review of proteomics · 2020Article
- Predicting antigen specificity of single T cells based on TCR CDR3 regions.Molecular systems biology · 2020Article
- Structure-guided engineering of the affinity and specificity of CARs against Tn-glycopeptides.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
- T-cell Receptors EngineeredCancer immunology research · 2019Article
- Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics.Seminars in cell & developmental biology · 2018Review
- Mapping Interaction Sites on Human Chemokine Receptors by Deep Mutational Scanning.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Subtle changes at the variable domain interface of the T-cell receptor can strongly increase affinity.The Journal of biological chemistry · 2018Article
- Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes.Journal of immunology (Baltimore, Md. : 1950) · 2017Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Utilizing a diverse binding site, T cell receptors (TCRs) specifically recognize a composite ligand comprised of a foreign peptide and a major histocompatibility complex protein (MHC). To help understand the determinants of TCR specificity, we studied a parental and engineered receptor whose peptide specificity had been switched via molecular evolution. Altered specificity was associated with a significant change in TCR-binding geometry, but this did not impact the ability of the TCR to signal in an antigen-specific manner. The determinants of binding and specificity were distributed among contact and non-contact residues in germline and hypervariable loops, and included disruption of key TCR-MHC interactions that bias αβ TCRs toward particular binding modes. Sequence-fitness landscapes identified additional mutations that further enhanced specificity. Our results demonstrate that TCR specificity arises from the distributed action of numerous sites throughout the interface, with significant implications for engineering therapeutic TCRs with novel and functional recognition properties.
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Registered trials
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