dc.contributor.advisor | Walter, Lutz Prof. Dr. | de |
dc.contributor.author | Hermes, Meike | de |
dc.date.accessioned | 2012-10-22T18:36:24Z | de |
dc.date.accessioned | 2013-01-18T14:27:25Z | de |
dc.date.available | 2013-01-30T23:50:19Z | de |
dc.date.issued | 2012-10-22 | de |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-000D-F0C1-A | de |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-3271 | |
dc.description.abstract | Rhesusaffen stellen ein wichtiges
Tiermodell für humane NK-Zell-assoziierte Krankheiten dar. Die
genetische Variabilität von KIR ist bereits beschrieben, allerdings
fehlen bisher jegliche Informationen über die Proteinexpression
aufgrund fehlender Antikörper. Daher wurden im Rahmen dieser Arbeit
monoklonale anti-Rhesusaffen KIR Antikörper etabliert und
charakterisiert. Mit Hilfe verschiedener Methoden (ELISA,
Durchflusszytometrie, Immunoblot) wurde die Spezifität
verschiedener Antikörper bestimmt. Neben Antikörpern mit einer
breiten Reaktivität für verschiedene KIR, konnten zudem Antikörper
mit einer mittleren und hohen Spezifität für einzelne KIR Moleküle
etabliert werden. Eine Epitopkartierung zeigte ein konformationales
Epitop für alle analysierten Antikörper. Zur Durchführung von
Vielfarben-Durchflusszytometrie wurden die Antikörper mit einem
Fluoreszenzfarbstoff markiert und Lymphozyten verschiedener
Rhesusaffen auf ihre KIR Expression untersucht. Es konnte ein
klonales KIR-Expressionsmuster, ähnlich dem humaner Lymphozyten (NK
und T Zellen), gezeigt werden. Zudem unterschieden sich
verschiedene Individuen in der Anzahl KIR-positiver Zellen: 29-78 %
aller NK Zellen waren KIR positiv unter der Verwendung eines breit
reagierenden Antikörpers, 2-56 % aller NK Zellen unter Verwendung
eines hoch spezifischen Antikörpers. 12-27 % aller CD8+ αβ T Zellen
und 6-58 % aller γδ T Zellen zeigten KIR-Expression. | de |
dc.format.mimetype | application/pdf | de |
dc.language.iso | eng | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | de |
dc.title | Characterisation of killer immunoglobulin-like receptors in rhesus macaques (Macaca mulatta) | de |
dc.type | doctoralThesis | de |
dc.title.translated | Charakterisierung von killer immunoglobulin-like receptors von Rhesus Affen (Macaca mulatta) | de |
dc.contributor.referee | Walter, Lutz Prof. Dr. | de |
dc.date.examination | 2012-07-13 | de |
dc.subject.dnb | 570 Biowissenschaften | de |
dc.subject.dnb | Biologie | de |
dc.subject.gok | WF 200 | de |
dc.subject.gok | MED 340 | de |
dc.description.abstracteng | Rhesus macaques are important animal
models of human diseases in which NK cells play significant roles.
Whereas data on KIR genetic variability were recently published,
data on KIR protein expression was not available until now due to
lack of specific (or cross‐reactive) antibodies. Therefore, mouse
monoclonal antibodies against one activating and two inhibitory
rhesus macaque KIR3D molecules were established and characterised.
Specificity of the obtained antibodies was determined using various
rhesus macaque KIR‐Fc fusion proteins (ELISA), cells transfected
with single rhesus macaque KIR genes as well as lymphocytes of
KIR‐typed rhesus macaques (flow cytometry). Besides broadly
reacting ones, also antibodies with intermediate and with high
specificity for single KIRs were obtained. Epitope mapping revealed
a conformational epitope for all analysed antibodies. The
antibodies were conjugated with suitable dyes and multicolour flow
cytometry was performed with lymphocytes from different rhesus
macaque individuals. The analysis revealed a clonal expression
pattern of rhesus macaque KIR that is similar to human KIR.
Differences were seen between individuals: 29‐78 % of NK cells were
positive with a pan‐KIR antibody, whereas 2‐56 % of NK cells were
positive with antibodies specific for single KIRs. For T cell
subpopulations 12‐27 % of all CD8+ αβ T cells and 6‐58 % of all γδ
T cells reacted specifically with the pan‐specific KIR antibody.
Also T cells expressed KIR at a clonal expression pattern using
antibodies specific for single KIRs. Similar results were obtained
with lymphocytes from cynomolgus macaques, baboons and African
green monkeys. Analysis of blood samples from SIV‐infected rhesus
macaques identified changes in the number of KIR‐expressing cells
during the acute phase of infection. KIR‐expressing NK cells were
decreased in animals with low viral load and in elite controllers,
whereas for γδ T cells an increase could be detected. In
conclusion, the established monoclonal antibodies are important
tools for future studies in which the role of NK cells in
infectious and autoimmune diseases are studied in macaques or other
Old World monkeys. | de |
dc.contributor.coReferee | Lübke, Torben Prof. Dr. | de |
dc.subject.topic | Göttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB) | de |
dc.subject.ger | Killer cell immunoglobulin like Rezeptoren (KIR) | de |
dc.subject.ger | Rhesusaffe (Macaca mulatta) | de |
dc.subject.ger | NK Zelle | de |
dc.subject.eng | killer cell immunoglobulin like receptors (KIR) | de |
dc.subject.eng | rhesus macaque (Macaca mulatta) | de |
dc.subject.eng | NK cell | de |
dc.subject.bk | 42.32 | de |
dc.subject.bk | 42.12 | de |
dc.subject.bk | 42.63 | de |
dc.subject.bk | 44.45 | de |
dc.identifier.urn | urn:nbn:de:gbv:7-webdoc-3745-8 | de |
dc.identifier.purl | webdoc-3745 | de |
dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften und Molekulare Biowissenschaften (GGNB) | de |
dc.identifier.ppn | 734091540 | de |