The impact of donor natural killer cell alloreactivity on allogeneic hematopoietic transplantation

Although natural killer (NK) cells are triggered to kill by many activating receptors, lysis of autologous cells is blocked by inhibitory receptors (called Killer cell Ig-like receptors or KIRs) which recognize epitopes shared by certain major histocompatibility complex (MHC) class I allele groups (called KIR ligands). As these inhibitory receptors are clonally distributed, they constituted a repertoire containing different allospecificities. Thus, the NK cells in the repertoire are lytic against allogeneic targets that do not express their inhibitory KIR ligands. In hematopoietic human-leukocyte-antigen (HLA)-haplotype mismatched transplantation, donor-vs-recipient alloreactive NK cells improve engraftment, decrease the incidence of leukemia relapse and do not cause Graft-vs-Host disease (GvHD). Pre-transplant molecular high-resolution HLA of recipient and donor, KIR genotyping of the donor and direct assessment of the donor NK repertoire identify donors with the potential for donor-vs-recipient NK cell alloreactivity.