ArticleMolecular immunology2010
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
Article in Molecular immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- Backbone Modifications of HLA-A2-Restricted Antigens Induce Diverse Binding and T Cell Activation Outcomes.Journal of the American Chemical Society · 2021Article
- 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
- Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Tuning T Cell Signaling Sensitivity Alters the Behavior of CD4Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- 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
- Force-Regulated In Situ TCR-Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC.Nature immunology · 2014Article
- T-cell receptor (TCR)-peptide specificity overrides affinity-enhancing TCR-major histocompatibility complex interactions.The Journal of biological chemistry · 2014Article
- Engineering improved T cell receptors using an alanine-scan guided T cell display selection system.Journal of immunological methods · 2013Article
- Subtle changes in TCRα CDR1 profoundly increase the sensitivity of CD4 T cells.Molecular immunology · 2013Article
- Diversity-oriented approaches for interrogating T-cell receptor repertoire, ligand recognition, and function.Immunological reviews · 2012Review
- Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR:epitope peptide affinity but not epitope peptide:MHC class I binding.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- A mathematical framework for analyzing T cell receptor scanning of peptides.Biophysical journal · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Interactions between the T cell receptor and cognate peptide-MHC are crucial initiating events in the adaptive immune response. These binding events are highly specific yet occur with micromolar affinity. Even weaker interactions between TCR and self-pMHC complexes play critical regulatory roles in T cell development, maintenance and coagonist activity. Due to their low-affinity, the kinetics and thermodynamics of such weak interactions are difficult to study. In this work, we used M15, a high-affinity TCR engineered from the 3.L2 TCR system, to study the binding properties, thermodynamics, and specificity of two altered peptide ligands (APLs). Our affinity measurements of the high-affinity TCR support the view that the wild type TCR binds these APLs in the millimolar affinity range, and hence very low affinities can still elicit biological functions. Finally, single methylene differences among the APLs gave rise to strikingly different binding thermodynamics. These minor changes in the pMHC antigen were associated with significant and unpredictable changes in both the entropy and enthalpy of the reaction. As the identical TCR was analyzed with several structurally similar ligands, the distinct thermodynamic binding profiles provide a mechanistic perspective on how exquisite antigen specificity is achieved by the T cell receptor.
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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.