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Immunomodulation using two types of ligands
Adámek, David ; Bezouška, Karel (advisor) ; Pompach, Petr (referee)
CD69 and NKR-P1 are receptors belonging to C-lectin family of receptors. We have recently identified two types of effective ligands for these receptors: dimeric N-acetyl-D-glukosamines (activators) and (calix[4]arenes) inhibitors. By using them, we can modulate immune response. First class of ligands (N-acetyl-D-glukosamines) is able to bind to CD69 and NKR-P1 and activate the cells. Second class of ligands (calix[4]arenes) is able to effectively inhibit functions of CD69, but not functions of NKR-P1. The aim of this study was to learn how to modulate immune response by various combinations of these compounds, and to explore their concentrations suitable for tumor therapies. Effect of used ligand and their combinations was studied in standard tests of cell proliferation, cell death and cytotoxic killing.
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Studies on NKR-P1A and NKR-P1B receptors expressed in eukaryotic organisms
Ivanova, Lyubina ; Bezouška, Karel (advisor) ; Rychlovský, Petr (referee)
NK (natural killer) cells, with their ability to identify antigens and extraneous substances, available in the organism through various moleculary receptors, are an important component of the immune system. The NKR-P1A and NKR-P1B proteins belong to the lectin receptors of natural killer cells. Primary ligands of lectin receptors comprise terminal oligosaccharides of glycoproteins on the surface of target (e.g. tumor) cells. The interaction between carbohydrate structures on the surface of antigens and their binding partners on NK receptors is followed by triggering the effector function of NK cells against the targets. The NK cells and NK receptors findings and their interactions with ligands are greatly utilized in the treatment of cancer, viral and autoimmune diseases. Heterologous protein production in the eukaryotic organism brings a lot of advantages. Unlike the prokaryotic organism, the methylotrophic yeast Pichia pastoris has the capability of performing many posttranslational modifications resulting in production of biological active protein molecule. Usually, the P. pastoris expression system disposes of high level protein expression and is also generally regarded as being faster, easier, and less expensive to use than expression systems derived from other eukaryotes. In this thesis, I...
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Investigation of the molecular mechanisms of elimination of clinically relevant tumors by killer cells of the immune system.
Libigerová, Martina ; Bezouška, Karel (advisor) ; Bosáková, Zuzana (referee)
Carbohydrates have an essentials role in wide range of biological phenomena. It is well known that most of the eukaryotic proteins are glycosylated and that their glycosylation undergoes dynamic changes, nevertheless the biological imperative for these modifications is still not fully understood. However, one area in which the importace of cell surface glycosylation has recently been the subject of active investigations is the tumor plasma membrane biology, where many changes in glycosylation have been found useful for diagnosis, and mostly recent, even for the therapies of malignant disease. Interestingly cell surface glycoconjugates, namely N-linked and O-linked oligosaccharides have been found therapeutically attractive for treatment of certain tumors. And although our understanding of the participation of these principal glycan classes in tumorigenesis is far from complete, there are already several examples of carbohydrate-based antitumor vaccines. Therefore, we decided to give this issue more attention, especially the molecular mechanisms responsible for identifying changes in glycosylation of the surface of tumor cells of the immune system. Although in the past in our laboratory identified a receptor-type lectin specific lectin receptors on natural killer cells, very little is yet known...
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