Coengagement of NKG2D, 2B4, and LFA-1 induces natural cytotoxicity by resting NK cells. Resting NK cells were mixed with (A) S2 (□), S2–ICAM-1 (), S2-CD48-ULBP1 (△), or S2–ICAM-1–CD48–ULBP1 (○) cells, or (B) S2 cells as in panel A preincubated with a rabbit serum raised against S2 cells (■, ♦, ▲, ●). Cells were incubated for 3 hours at 37°C. Specific lysis of S2 cells was calculated from the percentage of propidium iodide–positive S2 cells in duplicate samples, as determined by flow cytometry. The experiment is representative of 3 or more independent experiments.