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Murine xenograft bioreactors for human immunopeptidome discovery

The study of peptides presented by MHC class I and class II molecules is limited by the need for relatively large cell numbers, especially when studying post-translationally modified or otherwise rare peptide species. To overcome this problem, we pose the hypothesis that human cells grown as xenogra...

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Autores principales: Heather, James M., Myers, Paisley T., Shi, Feng, Aziz-Zanjani, Mohammad Ovais, Mahoney, Keira E., Perez, Matthew, Morin, Benjamin, Brittsan, Christine, Shabanowitz, Jeffrey, Hunt, Donald F., Cobbold, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898210/
https://www.ncbi.nlm.nih.gov/pubmed/31811195
http://dx.doi.org/10.1038/s41598-019-54700-2
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author Heather, James M.
Myers, Paisley T.
Shi, Feng
Aziz-Zanjani, Mohammad Ovais
Mahoney, Keira E.
Perez, Matthew
Morin, Benjamin
Brittsan, Christine
Shabanowitz, Jeffrey
Hunt, Donald F.
Cobbold, Mark
author_facet Heather, James M.
Myers, Paisley T.
Shi, Feng
Aziz-Zanjani, Mohammad Ovais
Mahoney, Keira E.
Perez, Matthew
Morin, Benjamin
Brittsan, Christine
Shabanowitz, Jeffrey
Hunt, Donald F.
Cobbold, Mark
author_sort Heather, James M.
collection PubMed
description The study of peptides presented by MHC class I and class II molecules is limited by the need for relatively large cell numbers, especially when studying post-translationally modified or otherwise rare peptide species. To overcome this problem, we pose the hypothesis that human cells grown as xenografts in immunodeficient mice should produce equivalent immunopeptidomes as cultured cells. Comparing human cell lines grown either in vitro or as murine xenografts, we show that the immunopeptidome is substantially preserved. Numerous features are shared across both sample types, including peptides and proteins featured, length distributions, and HLA-binding motifs. Peptides well-represented in both groups were from more abundant proteins, or those with stronger predicted HLA binding affinities. Samples grown in vivo also recapitulated a similar phospho-immunopeptidome, with common sequences being those found at high copy number on the cell surface. These data indicate that xenografts are indeed a viable methodology for the production of cells for immunopeptidomic discovery.
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spelling pubmed-68982102019-12-12 Murine xenograft bioreactors for human immunopeptidome discovery Heather, James M. Myers, Paisley T. Shi, Feng Aziz-Zanjani, Mohammad Ovais Mahoney, Keira E. Perez, Matthew Morin, Benjamin Brittsan, Christine Shabanowitz, Jeffrey Hunt, Donald F. Cobbold, Mark Sci Rep Article The study of peptides presented by MHC class I and class II molecules is limited by the need for relatively large cell numbers, especially when studying post-translationally modified or otherwise rare peptide species. To overcome this problem, we pose the hypothesis that human cells grown as xenografts in immunodeficient mice should produce equivalent immunopeptidomes as cultured cells. Comparing human cell lines grown either in vitro or as murine xenografts, we show that the immunopeptidome is substantially preserved. Numerous features are shared across both sample types, including peptides and proteins featured, length distributions, and HLA-binding motifs. Peptides well-represented in both groups were from more abundant proteins, or those with stronger predicted HLA binding affinities. Samples grown in vivo also recapitulated a similar phospho-immunopeptidome, with common sequences being those found at high copy number on the cell surface. These data indicate that xenografts are indeed a viable methodology for the production of cells for immunopeptidomic discovery. Nature Publishing Group UK 2019-12-06 /pmc/articles/PMC6898210/ /pubmed/31811195 http://dx.doi.org/10.1038/s41598-019-54700-2 Text en © The Author(s) 2019 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
Heather, James M.
Myers, Paisley T.
Shi, Feng
Aziz-Zanjani, Mohammad Ovais
Mahoney, Keira E.
Perez, Matthew
Morin, Benjamin
Brittsan, Christine
Shabanowitz, Jeffrey
Hunt, Donald F.
Cobbold, Mark
Murine xenograft bioreactors for human immunopeptidome discovery
title Murine xenograft bioreactors for human immunopeptidome discovery
title_full Murine xenograft bioreactors for human immunopeptidome discovery
title_fullStr Murine xenograft bioreactors for human immunopeptidome discovery
title_full_unstemmed Murine xenograft bioreactors for human immunopeptidome discovery
title_short Murine xenograft bioreactors for human immunopeptidome discovery
title_sort murine xenograft bioreactors for human immunopeptidome discovery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898210/
https://www.ncbi.nlm.nih.gov/pubmed/31811195
http://dx.doi.org/10.1038/s41598-019-54700-2
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