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Kinetics of antigen expression and epitope presentation during virus infection

Croft, Nathan P.; Smith, Stewart A.; Wong, Yik Chun; Tan, Chor Teck; Dudek, Nadine L.; Flesch, Inge E. A.; Lin, Leon C. W.; Tscharke, David C.; Purcell, Anthony W.

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Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as...[Show more]

dc.contributor.authorCroft, Nathan P.
dc.contributor.authorSmith, Stewart A.
dc.contributor.authorWong, Yik Chun
dc.contributor.authorTan, Chor Teck
dc.contributor.authorDudek, Nadine L.
dc.contributor.authorFlesch, Inge E. A.
dc.contributor.authorLin, Leon C. W.
dc.contributor.authorTscharke, David C.
dc.contributor.authorPurcell, Anthony W.
dc.date.accessioned2013-09-04T05:12:23Z
dc.date.available2013-09-04T05:12:23Z
dc.identifier.issn1553-7366
dc.identifier.issn1553-7374
dc.identifier.urihttp://hdl.handle.net/1885/10402
dc.description.abstractCurrent knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.
dc.description.sponsorshipNHMRC (National Health and Medical Research Council of Australia)
dc.format13 pages
dc.publisherPublic Library of Science
dc.rights"Copyright: 2013 Croft et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited" - 1st page of article
dc.sourcePLoS Pathogens 9.1 (2013): e1003129
dc.subjectvaccinia virus
dc.subjectCD8 T cells
dc.subjectantigen presentation
dc.subjectantigen-presenting cells
dc.subjectantigens
dc.subjectflow cytometry
dc.subjectprotein expression
dc.subjectT cells
dc.titleKinetics of antigen expression and epitope presentation during virus infection
dc.typeJournal article
local.description.notes"This work was funded by a Project Grant for the National Health and Medical Research Council of Australia (NH&MRC) project grant 1023141 and an Early Career Research grant from the University of Melbourne to N.P.C. This work was supported by infrastructure obtained through an Australian Research Council (ARC) Linkage Infrastructure and Equipment Grant (LE100100036). A.W.P. is an NHMRC Senior Research Fellow. D.C.T. is an ARC Future Fellow." - 1st page of article. Leon C. W. Lin also known as Chien-Wei Lin. Yik Chun Wong also known as Michael Wong
local.identifier.citationvolume9
dcterms.dateAccepted2012-11-26
dc.date.issued2013-01-31
local.identifier.absfor060500 - MICROBIOLOGY
local.identifier.ariespublicationf5625xPUB3876
local.publisher.urlhttp://www.plos.org/
local.type.statusPublished Version
local.contributor.affiliationCroft, Nathan P., Monash University, Department of Biochemistry and Molecular Biology
local.contributor.affiliationSmith, Stewart A., ANU, Research School of Biology, Division of Biomedical Science and Biochemistry
local.contributor.affiliationWong, Yik Chun, ANU, Research School of Biology, Division of Biomedical Science and Biochemistry
local.contributor.affiliationTan, Chor Teck, Monash University, Department of Biochemistry and Molecular Biology
local.contributor.affiliationDudek, Nadine L., Monash University, Department of Biochemistry and Molecular Biology
local.contributor.affiliationFlesch, Inge E. A., ANU, Research School of Biology, Division of Biomedical Science and Biochemistry
local.contributor.affiliationLin, Leon C. W., ANU, Research School of Biology, Division of Biomedical Science and Biochemistry
local.contributor.affiliationTscharke, David C., ANU, Research School of Biology, Division of Biomedical Science and Biochemistry
local.contributor.affiliationPurcell, Anthony W., Monash University, Department of Biochemistry and Molecular Biology
dc.relationhttp://purl.org/au-research/grants/nhmrc/1023141
dc.relationhttp://purl.org/au-research/grants/arc/ft110100310
dc.relationhttp://purl.org/au-research/grants/arc/le100100036
local.bibliographicCitation.issue1
local.identifier.doi10.1371/journal.ppat.1003129
dc.date.updated2015-12-11T08:30:28Z
local.identifier.scopusID2-s2.0-84875062998
local.identifier.thomsonID000314464600036
CollectionsANU Research Publications

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