Killing of allogeneic mDCs and T-cell blasts by KIR2DS1⁺ NK cells. KIR2DS1 expression in HSC donors increases the size of the alloreactive NK-cell subset during allogeneic HSCT. KIR2DS1 triggering by its KIR ligand (C2) promotes the ability of NK cells to limit GVHD and improve engraftment. (A) KIR2DS1⁺ clones coexpressing NKG2A kill both C2 homozygous and heterozygous T-cell blasts and mDCs. (B) KIR2DS1⁺ clones coexpressing KIR2DL2/L3 selectively kill C2 homozygous cells. (C) KIR2DS1⁺ clones coexpressing KIR3DL1 kill C2⁺ cells only when derived from Bw4 heterozygous (Bw4/Bw6) donors. In this case, NK cells preferentially killed T-cell blasts (+++) compared with mDCs (+). For each type of NK-target interaction the relevant KIR ligands (and/or HLA-E) recognized by the HLA class I–specific receptors expressed by the NK clones are shown. The box indicates the KIR-ligands responsible for licensing in the NK-cell donor.