ArticleProceedings of the National Academy of Sciences of the United States of America2000
In vitro evolution of a T cell receptor with high affinity for peptide/MHC.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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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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Who cites it
129 citing papers in PubMed, 292 citations in OpenAlex.
- Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to Enhance Stability, Pairing Fidelity, and Therapeutic Efficacy in TCR-T Cell Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment remodeling.Frontiers in immunology · 2026Article
- Article
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- De novo design and structure of a peptide-centric TCR mimic binding module.Science (New York, N.Y.) · 2025Article
- Mechano-pharmacology of T cell receptor specificity.Cell research · 2025Article
- Antigen-specific modulation of chronic experimental autoimmune encephalomyelitis in humanized mice by TCR-like antibody targeting autoreactive T-cell epitope.Life science alliance · 2025Article
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- HeteroTCR: A heterogeneous graph neural network-based method for predicting peptide-TCR interaction.Communications biology · 2024Article
- Deciphering Membrane-Protein Interactions and High-Throughput Antigen Identification with Cell Doublets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 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
- T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome.Nature reviews. Drug discovery · 2023Review
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
- A systematic safety pipeline for selection of T-cell receptors to enter clinical use.NPJ vaccines · 2023Article
- Measures of epitope binding degeneracy from T cell receptor repertoires.Proceedings of the National Academy of Sciences of the United States of America · 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
69 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
T cell receptors (TCRs) exhibit genetic and structural diversity similar to antibodies, but they have binding affinities that are several orders of magnitude lower. It has been suggested that TCRs undergo selection in vivo to maintain lower affinities. Here, we show that there is not an inherent genetic or structural limitation on higher affinity. Higher-affinity TCR variants were generated in the absence of in vivo selective pressures by using yeast display and selection from a library of Valpha CDR3 mutants. Selected mutants had greater than 100-fold higher affinity (K(D) approximately 9 nM) for the peptide/MHC ligand while retaining a high degree of peptide specificity. Among the high-affinity TCR mutants, a strong preference was found for CDR3alpha that contained Pro or Gly residues. Finally, unlike the wild-type TCR, a soluble monomeric form of a high-affinity TCR was capable of directly detecting peptide/MHC complexes on antigen-presenting cells. These findings prove that affinity maturation of TCRs is possible and suggest a strategy for engineering TCRs that can be used in targeting specific peptide/MHC complexes for diagnostic and therapeutic purposes.
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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.