A) NK-cell alloreactivity based on missing self-HLA. In HLA-mismatched HCT, educated donor NK cells stimulated by activating ligands, such as NKG2D ligand, are not inhibited from killing the target leukemia cell due to the lack of self-HLA ligand on the target cell. B) NK-cell alloreactivity based on missing ligand. In HLA-matched HCT, uneducated NK cells bearing KIR for which the patient lacks cognate HLA ligand can become activated under inflammatory conditions and can recognize and kill leukemic targets. C) NK-cell alloreactivity due to minimized inhibition and maximized activation. In HLA-matched HCT, educated donor NK-cells may experience less inhibition if the KIR-HLA interaction is characterized by low avidity. Heightened NK activity may occur if the donor NK cell expresses activating KIR.