MHC binding affects the dynamics of different T-cell receptors in different ways.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2005]-
    • Subject Terms:
      Histocompatibility Antigens*/chemistry ; Histocompatibility Antigens*/metabolism ; Receptors, Antigen, T-Cell*/chemistry ; Receptors, Antigen, T-Cell*/metabolism; Computational Biology ; Humans ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; Signal Transduction
    • 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.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Grant Information:
      MR/J002011/1 United Kingdom MRC_ Medical Research Council; 101799 United Kingdom WT_ Wellcome Trust; G9722488 United Kingdom MRC_ Medical Research Council; 207537/Z/17/Z United Kingdom WT_ Wellcome Trust; G19/31 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust
    • Accession Number:
      0 (Histocompatibility Antigens)
      0 (Receptors, Antigen, T-Cell)
    • Publication Date:
      Date Created: 20190910 Date Completed: 20200120 Latest Revision: 20220129
    • Publication Date:
      20240105
    • Accession Number:
      PMC6752857
    • Accession Number:
      10.1371/journal.pcbi.1007338
    • Accession Number:
      31498801