Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.

Fine mapping of human cytotoxic T lymphocyte (CTL) responses against hepatitis C virus (HCV) is based on external loading of target cells with synthetic peptides which are either derived from prediction algorithms or from overlapping peptide libraries. These strategies do not address putative host a...

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Autores principales: Benno Wölk, Claudia Trautwein, Benjamin Büchele, Nadine Kersting, Hubert E Blum, Hans-Georg Rammensee, Andreas Cerny, Stefan Stevanovic, Darius Moradpour, Volker Brass
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:4cef024f9f8245f98e0db5123e0d99a32021-11-18T07:31:09ZIdentification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.1932-620310.1371/journal.pone.0029286https://doaj.org/article/4cef024f9f8245f98e0db5123e0d99a32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22235280/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Fine mapping of human cytotoxic T lymphocyte (CTL) responses against hepatitis C virus (HCV) is based on external loading of target cells with synthetic peptides which are either derived from prediction algorithms or from overlapping peptide libraries. These strategies do not address putative host and viral mechanisms which may alter processing as well as presentation of CTL epitopes. Therefore, the aim of this proof-of-concept study was to identify naturally processed HCV-derived major histocompatibility complex (MHC) class I ligands. To this end, continuous human cell lines were engineered to inducibly express HCV proteins and to constitutively express high levels of functional HLA-A2. These cell lines were recognized in an HLA-A2-restricted manner by HCV-specific CTLs. Ligands eluted from HLA-A2 molecules isolated from large-scale cultures of these cell lines were separated by high performance liquid chromatography and further analyzed by electrospray ionization quadrupole time of flight mass spectrometry (MS)/tandem MS. These analyses allowed the identification of two HLA-A2-restricted epitopes derived from HCV nonstructural proteins (NS) 3 and 5B (NS3₁₄₀₆₋₁₄₁₅ and NS5B₂₅₉₄₋₂₆₀₂). In conclusion, we describe a general strategy that may be useful to investigate HCV pathogenesis and may contribute to the development of preventive and therapeutic vaccines in the future.Benno WölkClaudia TrautweinBenjamin BücheleNadine KerstingHubert E BlumHans-Georg RammenseeAndreas CernyStefan StevanovicDarius MoradpourVolker BrassPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29286 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Benno Wölk
Claudia Trautwein
Benjamin Büchele
Nadine Kersting
Hubert E Blum
Hans-Georg Rammensee
Andreas Cerny
Stefan Stevanovic
Darius Moradpour
Volker Brass
Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
description Fine mapping of human cytotoxic T lymphocyte (CTL) responses against hepatitis C virus (HCV) is based on external loading of target cells with synthetic peptides which are either derived from prediction algorithms or from overlapping peptide libraries. These strategies do not address putative host and viral mechanisms which may alter processing as well as presentation of CTL epitopes. Therefore, the aim of this proof-of-concept study was to identify naturally processed HCV-derived major histocompatibility complex (MHC) class I ligands. To this end, continuous human cell lines were engineered to inducibly express HCV proteins and to constitutively express high levels of functional HLA-A2. These cell lines were recognized in an HLA-A2-restricted manner by HCV-specific CTLs. Ligands eluted from HLA-A2 molecules isolated from large-scale cultures of these cell lines were separated by high performance liquid chromatography and further analyzed by electrospray ionization quadrupole time of flight mass spectrometry (MS)/tandem MS. These analyses allowed the identification of two HLA-A2-restricted epitopes derived from HCV nonstructural proteins (NS) 3 and 5B (NS3₁₄₀₆₋₁₄₁₅ and NS5B₂₅₉₄₋₂₆₀₂). In conclusion, we describe a general strategy that may be useful to investigate HCV pathogenesis and may contribute to the development of preventive and therapeutic vaccines in the future.
format article
author Benno Wölk
Claudia Trautwein
Benjamin Büchele
Nadine Kersting
Hubert E Blum
Hans-Georg Rammensee
Andreas Cerny
Stefan Stevanovic
Darius Moradpour
Volker Brass
author_facet Benno Wölk
Claudia Trautwein
Benjamin Büchele
Nadine Kersting
Hubert E Blum
Hans-Georg Rammensee
Andreas Cerny
Stefan Stevanovic
Darius Moradpour
Volker Brass
author_sort Benno Wölk
title Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
title_short Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
title_full Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
title_fullStr Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
title_full_unstemmed Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.
title_sort identification of naturally processed hepatitis c virus-derived major histocompatibility complex class i ligands.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/4cef024f9f8245f98e0db5123e0d99a3
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