Genomic Polymorphism and Allogeneic Hematopoietic Transplantation Outcome

Use of KIR and HLA-C type to predict GVL effects. NK alloreactivity in the GVH direction is depicted for 9 possible donor-recipient combinations of HLA-C (KIR) epitopes. For each combination, donors of 2 KIR types are considered: 1 having HLA-C^lys80–specific (KIR2DL1) and HLA-C^asn80–specific (KIR2DL3) KIRs and the other having only HLA-C^asn80–specific (KIR2DL3) KIRs. Shown for each donor are the subpopulations of NK cells that express KIR2DL1, KIR2DL3, or both and that use these receptors as their only inhibitory receptors for autologous major histocompatibility complex (MHC) class I molecules. For example, in the donor who is homozygous for HLA-C^lys80 but has only HLA-C^asn80–specific (KIR2DL3) KIRs, there are no NK cells using HLA-C–specific KIRs as their inhibitory receptors for autologous MHC class I molecules. NK cell subpopulations that are predicted to mediate GVL reactions are colored green (for go); those that are predicted to be inhibited by the recipient’s HLA-C type are colored red (for stop). The donor-recipient combinations for which knowledge of the HLA-C type is insufficient to predict the probability of a GVL effect, and for which knowledge of the KIR type is also required, are emphasized in bold. For simplicity, the additional HLA-C^asn80–specific KIR (KIR2DL2) is not included in this example, but similar considerations apply to it. The icons for KIRs and their cognate HLA-C ligands are color coded: KIR2DL1 and HLA-C^lys80 are shown in orange, and KIR2DL3 and HLA-C^asn80 are shown in purple. Reproduced with permission from Nature Reviews Immunology (5) © 2003 Macmillan Magazines Ltd. (http://www.nature.com/reviews).