Determination of donor-derived killer immunoglobulin-like receptor (KIR) by sequential genotyping in hematopoietic stem cell-transplanted patients

Donor killer immunoglobulin-like receptor (KIR) and KIR-ligand mismatch is considered vital in clarifying the mechanism of natural killer (NK) cell alloreactivity in hematopoietic stem cell transplantation (HSCT). In practical terms, however, it may be difficult to analyze the KIR genotype of donor cells directly as all donor cells are used for the transplant rather than for research purposes. To accurately estimate donor KIR genotype, we determined recipient KIR genotyping sequentially, at a minimum of two time points, using 19 KIR-specific primers in 10 patients who underwent HSCT. Among 10 patients, four had a KIR-ligand mismatch in the graft versus host direction. Sequential KIR genotyping showed the genotype changes at the time of engraftment (donor-derived) as well as relapse (recipient-derived). Our results highlight the utility of sequential KIR genotyping to better understand ligand-ligand, KIR-KIR, or ligand-KIR mismatches. Further studies, including a functional assay of NK cells may clarify the underlying mechanism of KIR ligand-donor KIR mismatch in HSCT.