Altering the specificity of NK:target cell interactions by genetic manipulation of NK receptor expression on primary mouse NK cells

Abstract A balance of signals generated via stimulatory and inhibitory NK receptors determines both target cell specificity and the outcome of NK–target cell interactions. The feasibility of introducing naturally occurring or genetically engineered chimeric NK receptors at the effector cell level may prove useful in NK cell-based immunotherapies. Here, we utilized a previously established lentiviral transduction system to over-express a model NKR-P1B inhibitory receptor on primary mouse NK cells. These genetically engineered NK cells became more sensitive to inhibitory signals delivered by target cells expressing the cognate NKR-P1B ligand, Ocil/Clr-b. This study demonstrated the utility of lentiviral vectors as a means to stably manipulate the target cell specificity of primary NK cells.