ArticleMolecular immunology2009
Engineering the binding properties of the T cell receptor:peptide:MHC ternary complex that governs T cell activity.
Article in Molecular immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- Enhanced T cell receptor specificity through framework engineering.Frontiers in immunology · 2024Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- Review
- 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-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation.Immuno-oncology technology · 2019Review
- Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Structure Based Prediction of Neoantigen Immunogenicity.Frontiers in 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
- A generalized framework for computational design and mutational scanning of T-cell receptor binding interfaces.Protein engineering, design & selection : PEDS · 2016Article
- Adoptive T Cell Therapies: A Comparison of T Cell Receptors and Chimeric Antigen Receptors.Trends in pharmacological sciences · 2016Review
- Recent advances in T-cell engineering for use in immunotherapy.F1000Research · 2016Review
- TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity.Current opinion in immunology · 2015Review
- Synthetic immunosurveillance systems: nanodevices to monitor physiological events.Biosensors & bioelectronics · 2014Review
- Specific increase in potency via structure-based design of a TCR.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Peptide-dependent conformational fluctuation determines the stability of the human leukocyte antigen class I complex.The Journal of biological chemistry · 2014Article
- Can we predict mutant neoepitopes in human cancers for patient-specific vaccine therapy?Cancer immunology research · 2014Review
- Plasticity in the contribution of T cell receptor variable region residues to binding of peptide-HLA-A2 complexes.Journal of molecular biology · 2013Article
- The same major histocompatibility complex polymorphism involved in control of HIV influences peptide binding in the mouse H-2Ld system.The Journal of biological chemistry · 2013Article
- Structure-Based, Rational Design of T Cell Receptors.Frontiers in immunology · 2013Review
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Authors and funding
7 authors.
Funding
Abstract
The potency of a T cell is determined in large part by two interactions, binding of a cognate peptide to the MHC, and binding of the T cell receptor (TCR) to this pepMHC. Various studies have attempted to assess the relative importance of these interactions, and to correlate the corresponding binding parameters with the level of T cell activity mediated by the peptide. To further examine the properties that govern optimal T cell activity, here we engineered both the peptide:MHC interaction and the TCR:pepMHC interaction to generate improved T cell activity. Using a system involving the 2C TCR and its allogeneic pepMHC ligand, QL9-L(d), we show that a peptide substitution of QL9 (F5R), increased the affinity and stability of the pep-L(d) complex (e.g. cell surface t(1/2)-values of 13 min for QL9-L(d) versus 87 min for F5R-L(d)). However, activity of peptide F5R for 2C T cells was not enhanced because the 2C TCR bound with very low affinity to F5R-L(d) compared to QL9-L(d) (K(D)=300 microM and K(D)=1.6 microM, respectively). To improve the affinity, yeast display of the 2C TCR was used to engineer two mutant TCRs that exhibited higher affinity for F5R-L(d) (K(D)=1.2 and 6.3 microM). T cells that expressed these higher affinity TCRs were stimulated by F5R-L(d) in the absence of CD8, and the highest affinity TCR exhibited enhanced activity for F5R compared to QL9. The results provide a guide to designing the explicit binding parameters that govern optimal T cell activities.
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