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Structural biology of receptor NKp44 and its ligand PCNA
Herynek, Štěpán ; Vaněk, Ondřej (advisor) ; Kubíčková, Božena (referee)
Natural killer cells (NK cells) are part of the immune system in human and other mammals. The task of these cells, which belong to the non-specific immunity, is to induce apoptosis in other cells of the body that may represent a threat for the body (i.e., tumour or virally infected cells). NK cells have a variety of surface receptors to recognize their target cells. A number of receptors are well-known today and they may be divided into groups based, e.g., on their structural similarities or on the type of signal which these receptors present to NK cells. Accordingly, we distinguish activation and inhibitory receptors. Inhibitory receptors inhibit NK cell response, while activation receptors elicit this response. During NK cell contact with another cell, the resulting NK cell behaviour is always the result of a certain balance of activation and inhibitory receptor responses. The NKp44 receptor is an immunoglobulin-like receptor. This receptor is very unique among other receptors in many respects, for example because it is associated with both activation and inhibitory motif. The ligand of this receptor is a proliferating cell nuclear antigen (PCNA). PCNA is a clamp protein important, inter alia, during DNA replication, in which it anchors other replisome proteins. This work is focused on...
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Recombinant preparation of proliferating cell nuclear antigen (PCNA)
Herynek, Štěpán ; Vaněk, Ondřej (advisor) ; Hlouchová, Klára (referee)
Natural killer (NK) cells are cells of native immunity. Their task is to recognize and destroy tumor cells or, for example, viruses infected cells. NK cells use a number of surface receptors to recognize affected cells. These receptors may be activating, i.e., activate the cytotoxic response of NK cells leading to the induction of apoptosis in the target cell, or inhibitory ones, which, on the other hand, inhibit NK cell response. Whether a cytotoxic response occurs depends on both types of NK receptors. The NKp44 receptor belongs to the family of immunoglobulin receptors and it is one of the activating receptors. Its properties are very unique among other receptors. Other activating receptors of the immunoglobulin receptor family are NKp46 and NKp30. Recently, the interaction between the NKp44 receptor and the proliferating cell nuclear antigen (PCNA) has been described. PCNA is a clamp protein that plays a key role in DNA replication and repair as it anchors replication proteins. This work focuses on the production and optimization of a production of PCNA and on the preparation of expression vectors for the later production of NKp44 and NKp46. Interaction of NKp44 and PCNA will be investigated later. For the same reason, the expression vector for the NKp46 protein is also prepared in this work....
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