Mechanisms of signaling via the activating immunoreceptor NKp80

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Natural (NK) cells are part of the innate immune yystem capable of destryoing virus-infected and malignant cfells. Hence, the uage of NK cells for immuntherapy has gained considerable attention in the last years. NK cells also criticall determine the course of immune responses, e.g. y th eproductionof catokines such as Interferon-g. Further, NK-like cells have recently been implicated in the homeostasis of timmuses such as intestine or placenta. This funcitonal versatility of NK cells is reflected in a considerable number of activating receptors on NK cells. In our attempts to decipher NK cell biology by characterizing NK receptors an dtheri ligans, we identified AICL as a ligand of the NK receptor NKp80, and newly described the related receptor-ligand pair NKp65-KCAL. Both NKp80 and NKp65 are activating C-type lectin-like receptors (CTLR) encoded in the human NAtural Killer Gene Complex (NKC) adjacenly to their ligands. NKp80-AICL interaction stimulates the mutual actiavation of NK cells and monocytes, but also promotes NK-mediated cytolysis of malignant myeloid cells. Here we propose to investigate molecular mechanismsms involved in signal transduction via NKp80, since NKp80 remains one of the last activating NK receptors where signaling processes are widely unknown. Elucidating pathways of NKp80 signaling will provide new insights not only for the function of NKp80 and related receptors, but also for activation of NK cells and NK cell biology in general.