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Exploration of peptides bound to MHC class I molecules in melanoma.

Identifieur interne : 001711 ( PubMed/Corpus ); précédent : 001710; suivant : 001712

Exploration of peptides bound to MHC class I molecules in melanoma.

Auteurs : Antonia L. Pritchard ; Marcus L. Hastie ; Michelle Neller ; Jeffrey J. Gorman ; Chris W. Schmidt ; Nicholas K. Hayward

Source :

RBID : pubmed:25645385

English descriptors

Abstract

Advancements in high-resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13,829 peptides were identified; 83-87% of these were 8-11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; mRNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA-type binding prediction for 10,078 9/10 mer peptides assigned 88-95% to a patient-specific HLA subtype, revealing a disparity in strength of predicted binding. HLA-B*27-specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells.

DOI: 10.1111/pcmr.12357
PubMed: 25645385

Links to Exploration step

pubmed:25645385

Le document en format XML

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<name sortKey="Pritchard, Antonia L" sort="Pritchard, Antonia L" uniqKey="Pritchard A" first="Antonia L" last="Pritchard">Antonia L. Pritchard</name>
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<nlm:affiliation>Oncogenomics Research Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Qld, Australia.</nlm:affiliation>
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<name sortKey="Hastie, Marcus L" sort="Hastie, Marcus L" uniqKey="Hastie M" first="Marcus L" last="Hastie">Marcus L. Hastie</name>
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<name sortKey="Neller, Michelle" sort="Neller, Michelle" uniqKey="Neller M" first="Michelle" last="Neller">Michelle Neller</name>
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<name sortKey="Gorman, Jeffrey J" sort="Gorman, Jeffrey J" uniqKey="Gorman J" first="Jeffrey J" last="Gorman">Jeffrey J. Gorman</name>
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<name sortKey="Schmidt, Chris W" sort="Schmidt, Chris W" uniqKey="Schmidt C" first="Chris W" last="Schmidt">Chris W. Schmidt</name>
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<name sortKey="Hayward, Nicholas K" sort="Hayward, Nicholas K" uniqKey="Hayward N" first="Nicholas K" last="Hayward">Nicholas K. Hayward</name>
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<term>Cell Line, Tumor</term>
<term>Epitopes</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Histocompatibility Antigens Class I (metabolism)</term>
<term>Humans</term>
<term>Immunity</term>
<term>Mass Spectrometry</term>
<term>Melanoma (genetics)</term>
<term>Melanoma (immunology)</term>
<term>Molecular Sequence Data</term>
<term>Peptides (chemistry)</term>
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<term>Peptides (metabolism)</term>
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<term>Reproducibility of Results</term>
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<term>Immunity</term>
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<front>
<div type="abstract" xml:lang="en">Advancements in high-resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13,829 peptides were identified; 83-87% of these were 8-11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; mRNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA-type binding prediction for 10,078 9/10 mer peptides assigned 88-95% to a patient-specific HLA subtype, revealing a disparity in strength of predicted binding. HLA-B*27-specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells.</div>
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