Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants

One of the functions of HLA class I alleles is interaction with natural killer (NK) cells. Receptors termed killer immunoglobulin-like receptors (KIRs) on NK cells recognize groups of HLA class I alleles, and interaction between receptor and class I allele inhibits reactivity of the NK cell. Failure to recognize the appropriate KIR ligand on a mismatched cell can trigger NK cell elimination of that target cell. Recent analysis of haploidentical hematopoietic transplantations has shown a reduction of graft failure, graft-versus-host disease, and relapse in those with KIR ligand incompatibility in the graft-versus-host direction. In this study we analyzed the effect of KIR ligand incompatibility on outcomes of unrelated donor bone marrow transplantations. The data show no advantage for KIR ligand incompatibility in this clinical setting as assessed by HLA-Bw4 and HLA-C alleles. It is possible that there will be a benefit of NK cell alloreactivity if strategies of haploidentical transplantation are used: high stem cell doses, extensive T-cell depletion, and no postgrafting immune suppression.