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dc.contributor |
Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades |
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dc.contributor.author |
Yaciuk, Jane C.
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dc.contributor.author |
Skaley, Matthew
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dc.contributor.author |
Bardet, Wilfried
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Schafer, Danijela Mojsilovic
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dc.contributor.author |
Cate, Steven
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dc.contributor.author |
Stewart, Christopher J.
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McMurtrey, Curtis
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Jackson, Rico Buchli
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Olvera, Alex
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Cedeño, Samandhy
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Plana, Montserrat
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dc.contributor.author |
Mothe, B.
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dc.contributor.author |
Brander, Christian
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dc.contributor.author |
West, John T.
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dc.contributor.author |
Hildebrand, William
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dc.date.accessioned |
2014-11-13T11:02:34Z |
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dc.date.available |
2015-05-12T23:02:54Z |
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dc.date.created |
2014 |
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dc.date.issued |
2014 |
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dc.identifier.citation |
Yaciuk, J. C., Skaley, M., Bardet, W., Schafer, F., Mojsilovic, D., Cate, S., et al. (2014). Direct interrogation of viral peptides presented by the class I HLA of HIV-infected T cells. Journal of Virology, 88(22), 12992-13004. |
ca_ES |
dc.identifier.issn |
0022-538X |
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dc.identifier.uri |
http://hdl.handle.net/10854/3578 |
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dc.description.abstract |
Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity. |
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dc.format |
application/pdf |
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dc.format.extent |
14 p. |
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dc.language.iso |
eng |
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dc.publisher |
American Socity for Microbiology |
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dc.rights |
(c) American Society for Microbiology |
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dc.rights |
Tots els drets reservats |
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dc.subject.other |
Sida -- Tractament |
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dc.title |
Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells |
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dc.type |
info:eu-repo/semantics/article |
ca_ES |
dc.embargo.terms |
6 mesos |
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dc.identifier.doi |
https://doi.org/ 10.1128/JVI.01914-14 |
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dc.relation.publisherversion |
http://jvi.asm.org/content/88/22/12992.abstract |
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dc.rights.accessRights |
info:eu-repo/semantics/openAccess |
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dc.type.version |
info:eu-repo/publishedVersion |
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dc.indexacio |
Indexat a WOS/JCR |
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dc.indexacio |
Indexat a SCOPUS |
ca_ES |
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