Activation via NKG2D overcomes deficient missing-self responses by natural killer gene complex knockdown (NKC^KD) and B2m^−/− NK cells to tumor cells. (A-B) The cytotoxic potential of WT versus NKC^KD LAK cells against (A) YAC-1 and (B) RMA-S-Rae-1β target cells was assessed by ⁵¹Cr-release assay in the presence or absence of blocking anti-NKG2D. (C-D) Similarly, cytotoxicity of WT versus B2m^−/− LAK cells was assessed against (C) YAC-1 and (D) RMA-S-Rae-1β target cells in the presence or absence of blocking anti-NKG2D. The data are displayed as the mean ± SD percentage of chromium release from triplicate wells. (E-F) In vivo rejection of (E) RMA-S-Rae-1β relative to RMA cells or of (F) B2m^−/−Rae-1e^tg splenocytes relative to WT splenocytes was assessed. The mean rejection is indicated by a horizontal line. Each symbol represents the data from a single mouse. Data are representative of ≥ 3 similar experiments. Groups differed significantly as shown (***P < .001). (G) Splenocytes from the indicated mouse strains were used in cytotoxicity assays against ⁵¹Cr-labeled YAC-1 cells at the indicated effector-to-target ratios. The data are displayed as the mean ± SD of chromium release from triplicate wells. These experiments were performed with mice on the B6 background.