ArticleJournal of immunology (Baltimore, Md. : 1950)2009
The impact of TCR-binding properties and antigen presentation format on T cell responsiveness.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- Precision modeling of tumor antigen-specific T-cell responses in humanized mice for preclinical assessment of cancer immunotherapies.Journal for immunotherapy of cancer · 2026Article
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- T cell decision-making decodes the dynamic antigenic landscape.Frontiers in immunology · 2026Review
- A comparative mathematical modeling study of phenotypic approaches to T cell activation.Scientific reports · 2025Article
- Tuning TCR complex recruitment to the T cell antigen coupler (TAC) enhances TAC-T cell function.Scientific reports · 2025Article
- Integration of kinetic data into affinity-based models for improved T cell specificity prediction.Biophysical journal · 2024Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- 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
- Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants.Immunity · 2020Article
- Review
- T-cell-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation.Immuno-oncology technology · 2019Review
- High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions.Cancer immunology research · 2019Article
- Is TCR/pMHC Affinity a Good Estimate of the T-cell Response? An Answer Based on Predictions From 12 Phenotypic Models.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
- Altered Peptide Ligands Impact the Diversity of Polyfunctional Phenotypes in T Cell Receptor Gene-Modified T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.Cancer immunology, immunotherapy : CII · 2017Article
- Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes.Journal of immunology (Baltimore, Md. : 1950) · 2017Review
- Heterogeneity assessment of functional T cell avidity.Scientific reports · 2017Article
- Deep Mutational Scans as a Guide to Engineering High Affinity T Cell Receptor Interactions with Peptide-bound Major Histocompatibility Complex.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
TCR interactions with cognate peptide-MHC (pepMHC) ligands are generally low affinity. This feature, together with the requirement for CD8/CD4 participation, has made it difficult to dissect relationships between TCR-binding parameters and T cell activation. Interpretations are further complicated when comparing different pepMHC, because these can vary greatly in stability. To examine the relationships between TCR-binding properties and T cell responses, in this study we characterized the interactions and activities mediated by a panel of TCRs that differed widely in their binding to the same pepMHC. Monovalent binding of soluble TCR was characterized by surface plasmon resonance, and T cell hybridomas that expressed these TCR, with or without CD8 coexpression, were tested for their binding of monomeric and oligomeric forms of the pepMHC and for subsequent responses (IL-2 release). The binding threshold for eliciting this response in the absence of CD8 (K(D) = 600 nM) exhibited a relatively sharp cutoff between full activity and no activity, consistent with a switchlike response to pepMHC on APCs. However, when the pepMHC was immobilized (plate bound), T cells with the lowest affinity TCRs (e.g., K(D) = 30 microM) responded, even in the absence of CD8, indicating that these TCR are signaling competent. Surprisingly, even cells that expressed high-affinity (K(D) = 16 nM) TCRs along with CD8 were unresponsive to oligomers in solution. The findings suggest that to drive downstream T cell responses, pepMHC must be presented in a form that supports formation of appropriate supramolecular clusters.
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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.