ArticlePLoS computational biology2019
MHC binding affects the dynamics of different T-cell receptors in different ways.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.International journal of molecular sciences · 2024Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Identification and In Silico Characterization of a Conserved Peptide on Influenza Hemagglutinin Protein: A New Potential Antigen for Universal Influenza Vaccine Development.Nanomaterials (Basel, Switzerland) · 2023Article
- Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities.Cell systems · 2023Article
- Generation of neoantigen-specific T cells for adoptive cell transfer for treating head and neck squamous cell carcinoma.Oncoimmunology · 2021Article
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- TheProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The structural basis of T-cell receptor (TCR) activation: An enduring enigma.The Journal of biological chemistry · 2020Review
- T-Cell Receptor CDR3 Loop Conformations in Solution Shift the Relative Vα-Vβ Domain Distributions.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
T cells use their T-cell receptors (TCRs) to scan other cells for antigenic peptides presented by MHC molecules (pMHC). If a TCR encounters a pMHC, it can trigger a signalling pathway that could lead to the activation of the T cell and the initiation of an immune response. It is currently not clear how the binding of pMHC to the TCR initiates signalling within the T cell. One hypothesis is that conformational changes in the TCR lead to further downstream signalling. Here we investigate four different TCRs in their free state as well as in their pMHC bound state using large scale molecular simulations totalling 26 000 ns. We find that the dynamical features within TCRs differ significantly between unbound TCR and TCR/pMHC simulations. However, apart from expected results such as reduced solvent accessibility and flexibility of the interface residues, these features are not conserved among different TCR types. The presence of a pMHC alone is not sufficient to cause cross-TCR-conserved dynamical features within a TCR. Our results argue against models of TCR triggering involving conserved allosteric conformational changes.
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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.