Control of NK cell activation by distribution and mobility of ligands on target cells (134.16)

Abstract

Abstract Natural killer (NK) cells are large granular lymphocytes that comprise 5-15% of peripheral blood mononuclear cells and function through cytokine production or cytotoxicity. The response of NK cells to contact with other cells is regulated through many different receptor-ligand interactions. However, it is not clear yet to what extent the distribution and mobility of ligands anchored into the plasma membrane of target cells influence NK cell activation and immune synapse formation during NK-target cell interactions. To study the role of the distribution and mobility of ligands on target cells, and to avoid the use of toxic inhibitors such as cyclodextrin, cholesterol-auxotroph Drosophila cell line S2 was transfected with GPI-linked CD48 (the ligand of NK cell receptor 2B4) and ULBP1 (the ligand of NK cell receptor NKG2D) and grown in serum-free conditions to eliminate cholesterol-enriched domains. 2B4- and NKG2D-dependent activation of NK cells was altered when the ligands where expressed in cholesterol-free S2 cells, suggesting a role of target cell membrane micro-domains in the response of NK cells. Experiments are underway to test how the mobility of ligands on the target cell may influence recognition by NK cells.