CI/NKG2^- NK cells in B6 mice exhibit reduced responsiveness to NK-sensitive target cells. Splenocytes from poly(I:C)-treated β2m^-/-, B6, or B10.M mice were stimulated for 5 hours in the presence of brefeldin A with Con A–activated lymphoblasts from the designated mice or with tumor cell lines before staining the cells with mAbs specific for cell-surface markers and intracellular IFN-γ. Results are depicted as the percentage ± SEM (n = 3 mice) of IFN-γ⁺ cells in each subset (CI/NKG2⁺ or CI/NKG2^-). (A) CI/NKG2^- NK cells in B6 mice respond poorly to β2m^-/- lymphoblasts. Similar results were obtained in 5 independent experiments (P = .006 for the % IFN-γ⁺ cells in CI/NKG2⁺ versus CI/NKG2^-). (B) CI/NKG2^- NK cells in B10.M mice respond as well as CI/NKG2⁺ NK cells to β2m^-/- lymphoblasts or YAC-1 tumor cells. A repetition of the experiment yielded similar results. (C) CI/NKG2^- NK cells in B6 mice respond poorly to YAC-1 tumor cells. Results are representative of 3 experiments (P = .003 for CI/NKG2⁺ versus CI/NKG2^-). (D) CI/NKG2^- NK cells in B6 mice respond poorly to RMA tumor cell transductants expressing NKG2D ligands Rae1 or H60. Results are representative of 3 experiments (P < .001 for CI/NKG2⁺ versus CI/NKG2^-).