Figure 1.

Model situations that provoke natural killer (NK) cell alloreactivity. Models are depicted as used in the present review, adopted and modified from Symons and Fuchs (53). Details concerning the activation mechanism are provided in the text. (A) Missing-self model, also described as “killer-cell immunoglobulin-like receptors (KIR)-ligand mismatch” or “ligand-incompability model”: Potential alloreactivity in the graft-versus-host direction is predicted by investigation of human leukocyte antigen (HLA) on donor and recipient. An HLA for inhibitory KIR that is present in the donor lacks in the recipient. The presence of the respective inhibitory KIR in the donor is assumed but not verified. (B) Receptor–ligand mismatch: NK cells become activated in the graft-versus-host direction, if they have an inhibitory KIR, for which the HLA ligand in the recipient is missing. Thus, the NK cells are “uninhibited.” Other than in (A), KIR on donor cells and HLA on recipient cells are investigated, not “assumed.” (C) Missing ligand: If the presence of the respective inhibitory KIR is not evaluated, but assumed in a model where at least one HLA-ligand is missing (HLA-C1/2 or Bw4). Other than in (A), only HLA on recipient cells but not on donor cells are evaluated. (C) The presence of activating KIR predicts alloreactivity in the presence of the respective activating ligand. KIR haplotype B/x contains more activating KIR than KIR haplotype A/A.