ArticleThe Journal of biological chemistry2018
Peptide-MHC (pMHC) binding to a human antiviral T cell receptor induces long-range allosteric communication between pMHC- and CD3-binding sites.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Central T cell tolerance from sparse peptide sampling.Science advances · 2026Article
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- The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.Nature communications · 2025Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies.Nature biomedical engineering · 2024Article
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- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
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- Article
- Evaluation of Molecular Simulations and Deep Learning Prediction of Antibodies' Recognition of TRBC1 and TRBC2.Antibodies (Basel, Switzerland) · 2023Article
- Molecular mechanism of phosphopeptide neoantigen immunogenicity.Nature communications · 2023Article
- Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity.Nature communications · 2022Article
- Article
- Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor.Annals of the rheumatic diseases · 2022Article
- Article
- Fluctuations in T cell receptor and pMHC interactions regulate T cell activation.Journal of the Royal Society, Interface · 2022Article
- Using molecular dynamics simulations to interrogate T cell receptor non-equilibrium kinetics.Computational and structural biotechnology journal · 2022Article
- Height, but not binding epitope, affects the potency of synthetic TCR agonists.Biophysical journal · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
T cells generate adaptive immune responses mediated by the T cell receptor (TCR)-CD3 complex comprising an αβ TCR heterodimer noncovalently associated with three CD3 dimers. In early T cell activation, αβ TCR engagement by peptide-major histocompatibility complex (pMHC) is first communicated to the CD3 signaling apparatus of the TCR-CD3 complex, but the underlying mechanism is incompletely understood. It is possible that pMHC binding induces allosteric changes in TCR conformation or dynamics that are then relayed to CD3. Here, we carried out NMR analysis and molecular dynamics (MD) simulations of both the α and β chains of a human antiviral TCR (A6) that recognizes the Tax antigen from human T cell lymphotropic virus-1 bound to the MHC class I molecule HLA-A2. We observed pMHC-induced NMR signal perturbations in the TCR variable (V) domains that propagated to three distinct sites in the constant (C) domains: 1) the Cβ FG loop projecting from the Vβ/Cβ interface; 2) a cluster of Cβ residues near the Cβ αA helix, a region involved in interactions with CD3; and 3) the Cα AB loop at the membrane-proximal base of the TCR. A biological role for each of these allosteric sites is supported by previous mutational and functional studies of TCR signaling. Moreover, the pattern of long-range, ligand-induced changes in TCR A6 revealed by NMR was broadly similar to that predicted by the MD simulations. We propose that the unique structure of the TCR β chain enables allosteric communication between the TCR-binding sites for pMHC and CD3.
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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.