title: Toward an atomistic understanding of the immune synapse: large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex.
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.
authors.affiliation: Centre for Computational Science, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
authors.forename: Shunzhou
authors.initials: S
authors.lastname: Wan
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coveney
mesh_terms: D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins; D008956:Models, Chemical; D009038:Motion; D046912:Multiprotein Complexes / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism; D013601:T-Lymphocytes
chemical_list: D015704:CD4 Antigens; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011948:Receptors, Antigen, T-Cell