A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.

PloS One
Bernhard KnappMichelle M Epstein

Abstract

The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood. We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level o...Continue Reading

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Citations

Sep 29, 2012·Computational and Mathematical Methods in Medicine·Wolfgang SchreinerNevena Ilieva
Jun 28, 2011·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·B KnappP Bauer
Oct 4, 2011·Chemical & Pharmaceutical Bulletin·M D Iqbal MahmoodTyuji Hoshino
Dec 4, 2015·Journal of Chemical Information and Modeling·Bernhard Knapp, Charlotte M Deane
Mar 16, 2016·Molecular BioSystems·Michael KennWolfgang Schreiner
May 25, 2013·Journal of Computational Chemistry·Birgit HischenhuberBernhard Knapp
Jun 13, 2014·Journal of Computational Chemistry·Hung DienBernhard Knapp
Mar 1, 2015·Briefings in Bioinformatics·Bernhard KnappCharlotte M Deane
Mar 20, 2015·Journal of Molecular Recognition : JMR·Jonathan P Carrillo-VazquezAbsalom Zamorano-Carrillo
Apr 9, 2013·Computer Physics Communications·B HischenhuberB Knapp
Jun 18, 2011·BMC Bioinformatics·Bernhard KnappWolfgang Schreiner
Dec 25, 2019·Journal of Biomolecular Structure & Dynamics·Sunil Kumar Tripathi, Dinakar M Salunke
May 28, 2019·Frontiers in Immunology·Sean A Nelson, Andrea J Sant
Feb 26, 2019·Scientific Reports·Jose Luis Dominguez, Bernhard Knapp
Jun 29, 2021·Journal of Biomolecular Structure & Dynamics·Arne StrandJohann Deisenhofer

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Methods Mentioned

BETA
acetylation
flow cytometry
density gradient centrifugation
FACS

Software Mentioned

Visual Molecular Dynamics ( VMD
SCWRL
Gromacs
SPDBV

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