KIR2DS1 binding to HLA-C2 triggers IFN-γ production in alloreactive NK cells. NK cell clones from 4 HLA-C1⁺ individuals were screened for alloreactivity against HLA-C1–missing, HLA-C2/C2 PHA T-cell blasts. Alloreactive KIR2DL2/3⁺ clones that coexpressed KIR2DS1 obtained from each individual were pooled and incubated with NK-resistant HLA-C1/C2 DCs or NK-susceptible HLA-C1–missing, HLA-C2/C2 DCs, pulsed with LPS (A) or A fumigatus (B). IFN-γ release (mean ± SD) in the absence (squares) or presence (triangles) of an anti-KIR2DS1 F(ab′)₂ is shown. Each symbol represents IFN-γ release by NK cells from 1 individual.