RCC and melanoma cells are more susceptible to the cytotoxic effects of KIR-incompatible NK clones than KIR-matched lines. NK cells were enriched and then cloned by limiting dilution from the PBMCs of cancer patient St (homozygous for HLA-C group 2) or from healthy donors homozygous for HLA-C group 1. (A) NK cell line 8-5, expanded from a C-G1 homozygous healthy donor (KR0350), killed a significantly higher percentage of C-G2 homozygous KIR-incompatible EBV-LCL, melanoma, and RCC cells than KIR-matched autologous EBV-LCL or KIR-matched allogeneic C-G1 homozygous melanoma and RCC cells (B). (C) NK line S-8, expanded from a C-G1 homozygous patient with widely metastatic melanoma (St), killed a significantly higher percentage of KIR-mismatched C-G2 homozygous EBV-LCLs and melanoma cells than autologous KIR-matched EBV-LCL and melanoma cells, in which minimal cytotoxicity was observed. Mean values +SD of 3 samples are shown. (D) MORRC NK line 10, expanded from a C-G2 homozygous healthy donor (MORRC), was cytotoxic to KIR-incompatible C-G1 homozygous but not KIR-matched C-G2 homozygous targets.