NKG2D enhances the killing of target cells by male H-Y CD8^lo cells in both an MHC-restricted and non-MHC-restricted fashion. Purified CD8^hi and CD8^lo T cells (1 × 10⁶) were cultured with irradiated B6-Tap^-/- (1 × 10⁷) splenocytes + H-Y peptide (1 μM) and IL-2 (20 U/mL) for 4 days. (A) Day-4 activated cells were used as effectors in a CTL assay against RMA (H-2^b, Rae-1δ^-) or RMA-Rae-1δ (H-2^b, Rae-1δ⁺) cells at an effector-to-target ratio of 10 to 1 in the presence of the indicated concentrations of H-Y peptide. (B) Day-4 activated cells were used in a redirected CTL assay against FcR⁺ P815 targets in the presence of the indicated mAbs. Panel A was repeated 5 times with similar results. Error bars represent the standard deviation of triplicate cultures. ^*P < .002; ^**P < .04.