Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-4704
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dc.contributor.authorGarcia, Victor-
dc.contributor.authorRichter, Kirsten-
dc.contributor.authorGraw, Frederik-
dc.contributor.authorOxenius, Annette-
dc.contributor.authorRegoes, Roland R.-
dc.date.accessioned2018-09-13T06:57:50Z-
dc.date.available2018-09-13T06:57:50Z-
dc.date.issued2015-05-
dc.identifier.issn1553-7358de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/10516-
dc.description.abstractCytotoxic T lymphocytes (CTLs) are important agents in the control of intracellular pathogens, which specifically recognize and kill infected cells. Recently developed experimental methods allow the estimation of the CTL's efficacy in detecting and clearing infected host cells. One method, the in vivo killing assay, utilizes the adoptive transfer of antigen displaying target cells into the bloodstream of mice. Surprisingly, killing efficacies measured by this method are often much higher than estimates obtained by other methods based on, for instance, the dynamics of escape mutations. In this study, we investigated what fraction of this variation can be explained by differences in peptide loads employed in in vivo killing assays. We addressed this question in mice immunized with lymphocytic choriomeningitis virus (LCMV). We conducted in vivo killing assays varying the loads of the immunodominant epitope GP33 on target cells. Using a mathematical model, we determined the efficacy of effector and memory CTL, as well as CTL in chronically infected mice. We found that the killing efficacy is substantially reduced at lower peptide loads. For physiological peptide loads, our analysis predicts more than a factor 10 lower CTL efficacies than at maximum peptide loads. Assuming that the efficacy scales linearly with the frequency of CTL, a clear hierarchy emerges among the groups across all peptide antigen concentrations. The group of mice with chronic LCMV infections shows a consistently higher killing efficacy per CTL than the acutely infected mouse group, which in turn has a consistently larger efficacy than the memory mouse group. We conclude that CTL killing efficacy dependence on surface epitope frequencies can only partially explain the variation in in vivo killing efficacy estimates across experimental methods and viral systems, which vary about four orders of magnitude. In contrast, peptide load differences can explain at most two orders of magnitude.de_CH
dc.language.isoende_CH
dc.publisherPublic Library of Sciencede_CH
dc.relation.ispartofPLOS Computational Biologyde_CH
dc.rightshttp://creativecommons.org/licenses/by/4.0/de_CH
dc.subjectAdoptive transferde_CH
dc.subjectAnimalsde_CH
dc.subjectViral antigensde_CH
dc.subjectComputational biologyde_CH
dc.subjectImmunologic cytotoxicityde_CH
dc.subjectEpitopesde_CH
dc.subjectHost-pathogen interactionsde_CH
dc.subjectLymphocytic choriomeningitisde_CH
dc.subjectLymphocytic choriomeningitis virusde_CH
dc.subjectMajor histocompatibility complexde_CH
dc.subjectMicede_CH
dc.subjectPeptidesde_CH
dc.subjectCytotoxic T-lymphocytesde_CH
dc.subjectViral proteinsde_CH
dc.subjectImmunological modelsde_CH
dc.subject.ddc571: Physiologie und verwandte Themende_CH
dc.titleEstimating the in vivo killing efficacy of cytotoxic T lymphocytes across different peptide-MHC complex densitiesde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Angewandte Simulation (IAS)de_CH
dc.identifier.doi10.21256/zhaw-4704-
dc.identifier.doi10.1371/journal.pcbi.1004178de_CH
dc.identifier.pmid25933039de_CH
zhaw.funding.euNode_CH
zhaw.issue5de_CH
zhaw.originated.zhawNode_CH
zhaw.pages.end13de_CH
zhaw.pages.start1de_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume11de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.funding.snf315230-130855de_CH
Appears in collections:Publikationen Life Sciences und Facility Management

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