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Scrutinizing MHC-I Binding Peptides and Their Limits of Variation

Designed peptides that bind to major histocompatibility protein I (MHC-I) allomorphs bear the promise of representing epitopes that stimulate a desired immune response. A rigorous bioinformatical exploration of sequence patterns hidden in peptides that bind to the mouse MHC-I allomorph H-2K(b) is pr...

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Autores principales: Koch, Christian P., Perna, Anna M., Pillong, Max, Todoroff, Nickolay K., Wrede, Paul, Folkers, Gerd, Hiss, Jan A., Schneider, Gisbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674988/
https://www.ncbi.nlm.nih.gov/pubmed/23754940
http://dx.doi.org/10.1371/journal.pcbi.1003088
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author Koch, Christian P.
Perna, Anna M.
Pillong, Max
Todoroff, Nickolay K.
Wrede, Paul
Folkers, Gerd
Hiss, Jan A.
Schneider, Gisbert
author_facet Koch, Christian P.
Perna, Anna M.
Pillong, Max
Todoroff, Nickolay K.
Wrede, Paul
Folkers, Gerd
Hiss, Jan A.
Schneider, Gisbert
author_sort Koch, Christian P.
collection PubMed
description Designed peptides that bind to major histocompatibility protein I (MHC-I) allomorphs bear the promise of representing epitopes that stimulate a desired immune response. A rigorous bioinformatical exploration of sequence patterns hidden in peptides that bind to the mouse MHC-I allomorph H-2K(b) is presented. We exemplify and validate these motif findings by systematically dissecting the epitope SIINFEKL and analyzing the resulting fragments for their binding potential to H-2K(b) in a thermal denaturation assay. The results demonstrate that only fragments exclusively retaining the carboxy- or amino-terminus of the reference peptide exhibit significant binding potential, with the N-terminal pentapeptide SIINF as shortest ligand. This study demonstrates that sophisticated machine-learning algorithms excel at extracting fine-grained patterns from peptide sequence data and predicting MHC-I binding peptides, thereby considerably extending existing linear prediction models and providing a fresh view on the computer-based molecular design of future synthetic vaccines. The server for prediction is available at http://modlab-cadd.ethz.ch (SLiDER tool, MHC-I version 2012).
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spelling pubmed-36749882013-06-10 Scrutinizing MHC-I Binding Peptides and Their Limits of Variation Koch, Christian P. Perna, Anna M. Pillong, Max Todoroff, Nickolay K. Wrede, Paul Folkers, Gerd Hiss, Jan A. Schneider, Gisbert PLoS Comput Biol Research Article Designed peptides that bind to major histocompatibility protein I (MHC-I) allomorphs bear the promise of representing epitopes that stimulate a desired immune response. A rigorous bioinformatical exploration of sequence patterns hidden in peptides that bind to the mouse MHC-I allomorph H-2K(b) is presented. We exemplify and validate these motif findings by systematically dissecting the epitope SIINFEKL and analyzing the resulting fragments for their binding potential to H-2K(b) in a thermal denaturation assay. The results demonstrate that only fragments exclusively retaining the carboxy- or amino-terminus of the reference peptide exhibit significant binding potential, with the N-terminal pentapeptide SIINF as shortest ligand. This study demonstrates that sophisticated machine-learning algorithms excel at extracting fine-grained patterns from peptide sequence data and predicting MHC-I binding peptides, thereby considerably extending existing linear prediction models and providing a fresh view on the computer-based molecular design of future synthetic vaccines. The server for prediction is available at http://modlab-cadd.ethz.ch (SLiDER tool, MHC-I version 2012). Public Library of Science 2013-06-06 /pmc/articles/PMC3674988/ /pubmed/23754940 http://dx.doi.org/10.1371/journal.pcbi.1003088 Text en © 2013 Koch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Koch, Christian P.
Perna, Anna M.
Pillong, Max
Todoroff, Nickolay K.
Wrede, Paul
Folkers, Gerd
Hiss, Jan A.
Schneider, Gisbert
Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title_full Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title_fullStr Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title_full_unstemmed Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title_short Scrutinizing MHC-I Binding Peptides and Their Limits of Variation
title_sort scrutinizing mhc-i binding peptides and their limits of variation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674988/
https://www.ncbi.nlm.nih.gov/pubmed/23754940
http://dx.doi.org/10.1371/journal.pcbi.1003088
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