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Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design
The features of peptide antigens that contribute to their immunogenicity are not well understood. Although the stability of peptide-MHC (pMHC) is known to be important, current assays assess this interaction only for peptides in isolation and not in the context of natural antigen processing and pres...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726561/ https://www.ncbi.nlm.nih.gov/pubmed/33298915 http://dx.doi.org/10.1038/s41467-020-20166-4 |
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author | Jappe, Emma C. Garde, Christian Ramarathinam, Sri H. Passantino, Ethan Illing, Patricia T. Mifsud, Nicole A. Trolle, Thomas Kringelum, Jens V. Croft, Nathan P. Purcell, Anthony W. |
author_facet | Jappe, Emma C. Garde, Christian Ramarathinam, Sri H. Passantino, Ethan Illing, Patricia T. Mifsud, Nicole A. Trolle, Thomas Kringelum, Jens V. Croft, Nathan P. Purcell, Anthony W. |
author_sort | Jappe, Emma C. |
collection | PubMed |
description | The features of peptide antigens that contribute to their immunogenicity are not well understood. Although the stability of peptide-MHC (pMHC) is known to be important, current assays assess this interaction only for peptides in isolation and not in the context of natural antigen processing and presentation. Here, we present a method that provides a comprehensive and unbiased measure of pMHC stability for thousands of individual ligands detected simultaneously by mass spectrometry (MS). The method allows rapid assessment of intra-allelic and inter-allelic differences in pMHC stability and reveals profiles of stability that are broader than previously appreciated. The additional dimensionality of the data facilitated the training of a model which improves the prediction of peptide immunogenicity, specifically of cancer neoepitopes. This assay can be applied to any cells bearing MHC or MHC-like molecules, offering insight into not only the endogenous immunopeptidome, but also that of neoepitopes and pathogen-derived sequences. |
format | Online Article Text |
id | pubmed-7726561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77265612020-12-17 Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design Jappe, Emma C. Garde, Christian Ramarathinam, Sri H. Passantino, Ethan Illing, Patricia T. Mifsud, Nicole A. Trolle, Thomas Kringelum, Jens V. Croft, Nathan P. Purcell, Anthony W. Nat Commun Article The features of peptide antigens that contribute to their immunogenicity are not well understood. Although the stability of peptide-MHC (pMHC) is known to be important, current assays assess this interaction only for peptides in isolation and not in the context of natural antigen processing and presentation. Here, we present a method that provides a comprehensive and unbiased measure of pMHC stability for thousands of individual ligands detected simultaneously by mass spectrometry (MS). The method allows rapid assessment of intra-allelic and inter-allelic differences in pMHC stability and reveals profiles of stability that are broader than previously appreciated. The additional dimensionality of the data facilitated the training of a model which improves the prediction of peptide immunogenicity, specifically of cancer neoepitopes. This assay can be applied to any cells bearing MHC or MHC-like molecules, offering insight into not only the endogenous immunopeptidome, but also that of neoepitopes and pathogen-derived sequences. Nature Publishing Group UK 2020-12-09 /pmc/articles/PMC7726561/ /pubmed/33298915 http://dx.doi.org/10.1038/s41467-020-20166-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jappe, Emma C. Garde, Christian Ramarathinam, Sri H. Passantino, Ethan Illing, Patricia T. Mifsud, Nicole A. Trolle, Thomas Kringelum, Jens V. Croft, Nathan P. Purcell, Anthony W. Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title | Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title_full | Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title_fullStr | Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title_full_unstemmed | Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title_short | Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
title_sort | thermostability profiling of mhc-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726561/ https://www.ncbi.nlm.nih.gov/pubmed/33298915 http://dx.doi.org/10.1038/s41467-020-20166-4 |
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