Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells.

Optimal activation of T cells requires delivery of both antigenic and costimulatory signals. It is unclear, however, if the function of the natural killer (NK) cells is also modulated by these 2 signals. Here we report that efficient control of solid allogeneic tumors by NK cells depends on codelivery of both B7-1 and major histocompatibility complex (MHC) class I on the tumor cells. The codelivery is required for optimal expansion and effector function of NK cells in response to both melanoma and plasmocytoma that expressed allogeneic MHC class I. Our results demonstrate that the 2 signals required for T-cell function also can regulate NK immunity and reveal an important similarity between the innate NK response and the adaptive T-cell response.