Strukturní biochemie komplexu receptorů NKp30 a B7-H6 u lidských NK buněk

Skořepa, Ondřej

Natural killer cells (NK cells for short) are lymphocytes of the non-specific (innate) immune system. They excel in the ability to recognise and eliminate infected or cancerous cells rapidly. Although their role in immune surveillance of malignant transformation was confirmed years ago, ongoing research shows that this process is far from simple. NKp30 is one of the central activating receptors of NK cells with a potential for use in targeted immunotherapy. The oligomerisation of the extracellular ligand-recognition domain of NKp30 in solution depends on the presence of a C-terminal stalk region. However, the structure and role in signal transduction of these oligomers are still unclear. Moreover, the interaction of NKp30 with ligands is influenced by the presence of N-linked glycosylation. In this work, we investigated whether and how the oligomerisation of NKp30 depends on its glycosylation. Our results show that NKp30 forms oligomers, regardless of whether glycosylation is complex or uniform (acquired by expression in the HEK293S GnTI- cell line). In contrast, NKp30 was found to form only monomers when enzymatically deglycosylated. Furthermore, we characterised the interaction with the ligand B7-H6, again concerning oligomerisation and glycosylation. We solved the crystal structure of its...

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