First, we used the plate-bound model of exhaustion to demonstrate that simultaneous engagement of NKG2A during positive stimulation partially protected NK cells from the detrimental effects of prolonged activation, as evidenced by increases in cytotoxicity against leukemia targets and heightened expression of the effector molecules granzyme B and TRAIL, as well as proliferative index. The gene discussed is GZMB; the disease is leukemia.