Toward an atomistic understanding of the immune synapse: large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex

Shunzhou Wan, Darren R. Flower, Peter V. Coveney

Research output: Contribution to journalArticle

Abstract

T-cell activation requires interaction of T-cell receptors (TCR) with peptide epitopes bound by major histocompatibility complex (MHC) proteins. This interaction occurs at a special cell-cell junction known as the immune or immunological synapse. Fluorescence microscopy has shown that the interplay among one agonist peptide-MHC (pMHC), one TCR and one CD4 provides the minimum complexity needed to trigger transient calcium signalling. We describe a computational approach to the study of the immune synapse. Using molecular dynamics simulation, we report here on a study of the smallest viable model, a TCR-pMHC-CD4 complex in a membrane environment. The computed structural and thermodynamic properties are in fair agreement with experiment. A number of biomolecules participate in the formation of the immunological synapse. Multi-scale molecular dynamics simulations may be the best opportunity we have to reach a full understanding of this remarkable supra-macromolecular event at a cell-cell junction.
Original languageEnglish
Pages (from-to)1221-1230
Number of pages10
JournalMolecular Immunology
Volume45
Issue number5
Early online date5 Nov 2007
DOIs
Publication statusPublished - Mar 2008

Keywords

  • immunological synapse
  • molecular dynamics
  • high performance computing

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