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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Wan S,Flower DR,Coveney PV

doi

10.1016/j.molimm.2007.09.022

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

1221-30

issue

5

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(07)00770-5

journal_volume

45

pub_type

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