The MHC class I peptide repertoire is molded by the transcriptome

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a no...

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Main Authors: Fortier, Marie-Hélène, Caron, Étienne, Hardy, Marie-Pierre, Voisin, Grégory, Lemieux, Sébastien, Perreault, Claude, Thibault, Pierre
פורמט: Artigo
שפה:English
יצא לאור: The Rockefeller University Press 2008
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גישה מקוונת:https://ncbi.nlm.nih.gov/pmc/articles/PMC2275383/
https://ncbi.nlm.nih.gov/pubmed/18299400
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1084/jem.20071985
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spelling pubmed-22753832008-09-17 The MHC class I peptide repertoire is molded by the transcriptome Fortier, Marie-Hélène Caron, Étienne Hardy, Marie-Pierre Voisin, Grégory Lemieux, Sébastien Perreault, Claude Thibault, Pierre J Exp Med Articles Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells. The Rockefeller University Press 2008-03-17 /pmc/articles/PMC2275383/ /pubmed/18299400 http://dx.doi.org/10.1084/jem.20071985 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Articles
spellingShingle Articles
Fortier, Marie-Hélène
Caron, Étienne
Hardy, Marie-Pierre
Voisin, Grégory
Lemieux, Sébastien
Perreault, Claude
Thibault, Pierre
The MHC class I peptide repertoire is molded by the transcriptome
description Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.
author Fortier, Marie-Hélène
Caron, Étienne
Hardy, Marie-Pierre
Voisin, Grégory
Lemieux, Sébastien
Perreault, Claude
Thibault, Pierre
author_facet Fortier, Marie-Hélène
Caron, Étienne
Hardy, Marie-Pierre
Voisin, Grégory
Lemieux, Sébastien
Perreault, Claude
Thibault, Pierre
author_sort Fortier, Marie-Hélène
title The MHC class I peptide repertoire is molded by the transcriptome
title_short The MHC class I peptide repertoire is molded by the transcriptome
title_full The MHC class I peptide repertoire is molded by the transcriptome
title_fullStr The MHC class I peptide repertoire is molded by the transcriptome
title_full_unstemmed The MHC class I peptide repertoire is molded by the transcriptome
title_sort mhc class i peptide repertoire is molded by the transcriptome
publisher The Rockefeller University Press
publisher_facet The Rockefeller University Press
publishDate 2008
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2275383/
https://ncbi.nlm.nih.gov/pubmed/18299400
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1084/jem.20071985
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