ArticleThe Journal of biological chemistry2013
T-cell receptor specificity maintained by altered thermodynamics.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed.
- Review
- Quantitative nanoscale imaging shows peptide-MHC I complexes are monomeric and spatially regulated in human dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- 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
- Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes.iScience · 2025Article
- Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification and affinity enhancement of T-cell receptor targeting a KRASCommunications biology · 2024Article
- Therapeutic high affinity T cell receptor targeting a KRASNature communications · 2022Article
- ReliableJournal of chemical information and modeling · 2022Article
- Grouping T-Cell Antigen Receptors by Specificity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors.Nanoscale · 2021Article
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- Molecular Rules Underpinning Enhanced Affinity Binding of Human T Cell Receptors Engineered for Immunotherapy.Molecular therapy oncolytics · 2020Article
- T cell receptor interactions with human leukocyte antigen govern indirect peptide selectivity for the cancer testis antigen MAGE-A4.The Journal of biological chemistry · 2020Article
- Predicting antigen specificity of single T cells based on TCR CDR3 regions.Molecular systems biology · 2020Article
- Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.The Journal of clinical investigation · 2020Article
- TCR-induced alteration of primary MHC peptide anchor residue.European journal of immunology · 2019Article
- The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics.Seminars in cell & developmental biology · 2018Review
- The Hypervariable Loops of Free TCRs Sample Multiple Distinct Metastable Conformations in Solution.Frontiers in molecular biosciences · 2018Article
- Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes.Journal of immunology (Baltimore, Md. : 1950) · 2017Review
- Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8Nature structural & molecular biology · 2017Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The T-cell receptor (TCR) recognizes peptides bound to major histocompatibility molecules (MHC) and allows T-cells to interrogate the cellular proteome for internal anomalies from the cell surface. The TCR contacts both MHC and peptide in an interaction characterized by weak affinity (KD = 100 nM to 270 μM). We used phage-display to produce a melanoma-specific TCR (α24β17) with a 30,000-fold enhanced binding affinity (KD = 0.6 nM) to aid our exploration of the molecular mechanisms utilized to maintain peptide specificity. Remarkably, although the enhanced affinity was mediated primarily through new TCR-MHC contacts, α24β17 remained acutely sensitive to modifications at every position along the peptide backbone, mimicking the specificity of the wild type TCR. Thermodynamic analyses revealed an important role for solvation in directing peptide specificity. These findings advance our understanding of the molecular mechanisms that can govern the exquisite peptide specificity characteristic of TCR recognition.
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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.