Figure 2.

Models of natural killer (NK) cell alloreactivity after allo-SCT. Models of NK cell alloreactivity incorporate some or all of the following information: (1) high resolution HLA typing of donor and recipient;¹⁰³ (2) genotyping of the killer immunoglobulin-like receptor (KIR) locus by PCR of genomic DNA using sequence-specific oligonucleotide probes (SSP)¹⁰² and (3) phenotyping of KIR expression by flow cytometry using commercially available antibodies.¹⁰¹ (a) The ligand incompatibility model predicts NK cell alloreactivity in the graft-vs-host direction (depicted) when the recipient lacks expression of an HLA ligand for inhibitory KIR, in this case a member of the HLA-C1 group, that is present in the donor. The presence of functional donor NK cells expressing KIR2DL2, the receptor for molecules of the HLA-C1 group, is assumed in this model. (b) The receptor-ligand model predicts NK cell alloreactivity in the graft-vs-host direction when the recipient lacks an HLA ligand for donor inhibitory KIR, whose presence is verified by KIR genotyping and flow cytometry of donor NK cells. The HLA type of donor cells is irrelevant to this model. (c) The missing ligand model predicts NK cell alloreactivity in the graft-vs-host direction when recipient cells lacks expression of at least one of the HLA ligands (C1, C2 or -Bw4) for inhibitory KIR. (d) The KIR gene–gene model predicts NK alloreactivity when the donor and recipient are mismatched for KIR gene content. Inhibitory KIR genes are shown as unshaded boxes, whereas black boxes represent activating KIR genes. In the example shown, the recipients KIR genotype is said to be ‘included’ in the donor’s KIR genotype.¹⁰³