Identification of the cellular ligand of NKp44

• Applicant: Dr. Philip Kruse
• Subject Area: Cell Biology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217049376

This study aims at identifying the cellular ligand of NKp44. NKp44 belongs, beside NKp30 and NKp46, to the natural cytotoxicity receptors (NCRs) which are mainly expressed on the cell surface of natural killer (NK) cells. NCRs are playing an important role in the elimination of tumour and virus-infected cells.Some proteins are already known which can interact with the different NCRs. It was shown, for example, that NCRs can bind to heparin sulfates on tumour cells, also different virus proteins can interact with NCRs. Anyway, for these proteins only an interaction with NCRs was shown while a possible activation of primary NK cells was not analysed, though. Furthermore, none of these proteins are expressed by the cell itself and meaning they represent a cellular ligand. Only B7-H6 is as cellular ligand for NKp30 known whereas no cellular ligand is known for NKp44 and NKp46.The aim of this project is to identify this cellular ligand for NKp44. To identify tumour cell lines which express the NKp44 ligand on the cell surface soluble NKp44 fusion proteins and a NKp44 reporter cell line will be used. Those tumour cell lines will be transfected with siRNA/shRNA libraries to prevent the interaction with NKp44. By this way, molecules can be identified which are involved in the binding of NKp44. To prove these results, tumour cell lines which show no interaction with NKp44 will be trans-fected with the cDNA of the protein which seems to be involved in the binding. If a cell line gained the ability to interact with NKp44 it would prove the analysed protein to be a ligand or at least a co-ligand of NKp44.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professor Dr. Eric Vivier