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

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.