Nonlicensed NK cells expressing inhibitory KIR for non-self class I after TCD-HSCT are activated in response to leukemic cell lines and primary leukemic blasts lacking cognate ligands. Percentages of IFN-γ–producing cells among nonlicensed NK cells exclusively expressing the inhibitory KIR for non-self HLA class I ligand (NS-KIR) after activation by leukemic targets are shown for 2 patients. Targets include the patient-derived ALL cell line PhALL3.1 (HLA-C1/C1; Bw6/Bw6), the AML cell lines HL60 (HLA-C2/C2; Bw4/Bw6) and KASUMI-1 (HLA-C1/C1; Bw4/Bw6), and primary biphenotypic leukemic blasts PBL-1 (HLA-C1/C1; Bw4/Bw4). (A) Compared with the donor control, NK cells exclusively expressing NS-KIR KIR2DL3 from the HLA-C2/C2, Bw4/Bw4 post-HSCT patient (patient no. 5) are specifically activated against HL60, which lacks the cognate HLA-C1 ligand. (B) NK cells exclusively expressing NS-KIR KIR2DL1 from the HLA-C1/C1, Bw4/Bw4 post-HSCT recipient (patient no. 16) are activated against PhALL3.1, KASUMI-1, and PBL-1, which lack the cognate HLA-C2 ligand.