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

<h4>Background</h4>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 unde...

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Autores principales:	Bernhard Knapp, Ulrich Omasits, Wolfgang Schreiner, Michelle M Epstein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d098660f369a4e2b9ea570385f9b34dd
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spelling	oai:doaj.org-article:d098660f369a4e2b9ea570385f9b34dd2021-12-02T20:19:58ZA comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.1932-620310.1371/journal.pone.0011653https://doaj.org/article/d098660f369a4e2b9ea570385f9b34dd2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20657836/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Results</h4>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 of T cell regulation.Bernhard KnappUlrich OmasitsWolfgang SchreinerMichelle M EpsteinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11653 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bernhard Knapp Ulrich Omasits Wolfgang Schreiner Michelle M Epstein A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
description	<h4>Background</h4>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.<h4>Results</h4>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 of T cell regulation.
format	article
author	Bernhard Knapp Ulrich Omasits Wolfgang Schreiner Michelle M Epstein
author_facet	Bernhard Knapp Ulrich Omasits Wolfgang Schreiner Michelle M Epstein
author_sort	Bernhard Knapp
title	A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
title_short	A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
title_full	A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
title_fullStr	A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
title_full_unstemmed	A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
title_sort	comparative approach linking molecular dynamics of altered peptide ligands and mhc with in vivo immune responses.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/d098660f369a4e2b9ea570385f9b34dd
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A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.

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