DC ElementWertSprache
dc.contributor.advisorAltfeld, Marcus-
dc.contributor.advisorMeier, Chris-
dc.contributor.authorZiegler, Maja Christiane-
dc.date.accessioned2020-11-27T09:30:35Z-
dc.date.available2020-11-27T09:30:35Z-
dc.date.issued2020-
dc.identifier.urihttps://ediss.sub.uni-hamburg.de/handle/ediss/8705-
dc.description.abstractNatural killer cells (NK cells) are known to play a crucial role in the control of viral infections. It is described that inhibitory killer cell immunoglobuline-like receptors (KIRs) expressed on NK cells modulate NK cell activity through the binding to human leukocyte antigen class I (HLA-I). These interactions are influenced by viral infections altering intracellular peptide repertoires available for presentation by HLA-I. KIR2DL2/3 binds to HLA-C molecules, but the exact mechanisms how this interaction is modulated by viral infections remains incompletely understood. In the first part of this thesis, I investigated whether frequencies of KIR2DL2/3+ NK cells recognizing HLA-C*03:04/viral peptide complexes are impacted by Yellow Fever Virus vaccination and HIV-1 or HCV infection. Ex vivo HLA-I tetramer staining of primary human NK cells revealed that the proportion of teramer+KIR2DL2/3+ NK cells remained stable over time after antigen exposure and that the avidity of the tetramer to KIR2DL2/3 dictated the frequency of tetramer+KIR2DL2/3+ NK cells. In the second part, I focused on HIV-1-induced alterations in the HLA-I-presented peptide repertoire and how these changes modulate the function of NK cells. Using mass spectrometric analysis, I identified a total of 533 peptides exclusively presented on HIV-1-infected cells, of which only 0.2 % represented HIV-1-derived peptides. Cell-based in vitro assays focusing on HLA-C*03:04/KIR2DL3 interactions revealed that HLA-C*03:04-presented peptides derived from non-infected CD4+ T cells mediated stronger binding of inhibitory KIR2DL3 than peptides derived from HIV-1-infected cells. All in all these data show that interactions between inhibitory KIRs and their HLA-I ligands are modulated by the HLA-presented peptide, but that these interactions do not result in the expansion or accumulation of specific inhibitory KIR+ NK cell subpopulations. But, HIV-1-infection-induced changes in HLA-I-presented peptides can reduce engagement of inhibitory KIRs, providing a mechanism for enhanced activation of NK cells by virus-infected cells leading to a more favorable disease outcome.en
dc.language.isoende_DE
dc.publisherStaats- und Universitätsbibliothek Hamburg Carl von Ossietzkyde
dc.rightshttp://purl.org/coar/access_right/c_abf2de_DE
dc.subjectNK cellsen
dc.subjectHLA-Ien
dc.subjectKIR HIVen
dc.subjectHCVen
dc.subjectviral infectionen
dc.subjectHLA-I presented peptidesen
dc.subject.ddc570: Biowissenschaften, Biologiede_DE
dc.titleImpact of viral infections on Natural Killer cell frequencies and recognitionen
dc.title.alternativeEinfluss viraler Infektionen auf Frequenz und Erkennung Natürlicher Killerzellende
dc.typedoctoralThesisen
dcterms.dateAccepted2020-10-23-
dc.rights.cchttps://creativecommons.org/licenses/by/4.0/de_DE
dc.rights.rshttp://rightsstatements.org/vocab/InC/1.0/-
dc.subject.bcl42.32: Virologiede_DE
dc.type.casraiDissertation-
dc.type.dinidoctoralThesis-
dc.type.driverdoctoralThesis-
dc.type.statusinfo:eu-repo/semantics/publishedVersionde_DE
dc.type.thesisdoctoralThesisde_DE
tuhh.type.opusDissertation-
thesis.grantor.departmentChemiede_DE
thesis.grantor.placeHamburg-
thesis.grantor.universityOrInstitutionUniversität Hamburgde_DE
dcterms.DCMITypeText-
datacite.relation.IsSupplementedBy10.3389/fimmu.2018.02361de_DE
datacite.relation.IsSupplementedBy10.1097/QAD.0000000000002596de_DE
dc.identifier.urnurn:nbn:de:gbv:18-ediss-88293-
item.advisorGNDAltfeld, Marcus-
item.advisorGNDMeier, Chris-
item.creatorGNDZiegler, Maja Christiane-
item.languageiso639-1other-
item.grantfulltextopen-
item.creatorOrcidZiegler, Maja Christiane-
item.fulltextWith Fulltext-
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen
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