Expression of KIR2DS1 in the presence of HLA-C2 tunes down the responsiveness of NK cells educated via inhibitory HLA class I–specific NK-cell receptors. (A-C) Paired analyses of NK-cell degranulation after stimulation with K562 cells by NKG2A⁺KIR⁻ and NKG2A⁺KIR2DS1sp NK cells cultured overnight in (A) medium alone, (B) 10⁴ U IFN-α/mL, or (C) 10 ng/mL IL-15. (D-F) Paired analyses of NK-cell degranulation after stimulation with K562 cells by NKG2A⁻KIR2DL3sp and NKG2A⁻KIR2DL3sp NK cells coexpressing KIR2DS1 cultured overnight in (D) medium alone, (E) 10⁴ U IFN-α/mL, or (F) 10 ng/mL IL-15. (G-I) Paired analyses of NK-cell degranulation after stimulation with K562 cells by NKG2A⁻KIR2DL1sp and NKG2A⁻KIR2DL1sp NK cells coexpressing KIR2DS1 cultured overnight in (G) medium alone,(H) 10⁴ U IFN-α/mL, or (I) 10 ng/mL IL-15. P values indicate a statistically significant difference between groups, tested by a Wilcoxon matched-pairs test.