Background and Objectives Natural Killer (NK) cells are capable of recognizing target cells altered by pathologic states such as viral infection and malignant transformation. The NK cell’s capacity to recognize and kill abnormal cells while sparing normal cells relies on the integration of activating signals and tolerance to cells expressing self-MHC molecules. Our understanding of how NK receptors mediate these signals and control NK cell function has advanced to the point where models of NK biology can be tested and revised in the clinical setting of hematopoietic stem cell transplantation.
Materials and Methods This review article highlights several of the seminal contributions to the field of NK biology and their relevance to allogeneic and autologous hematopoietic cell transplantation.
Results and Conclusions Inhibitory NK receptors are critical for achieving tolerance to cells expressing self-MHC molecules and recognizing target cells lacking self-MHC class I molecules. Activating NK receptors can circumvent NK tolerance and directly signal activation. Both inhibitory and activating receptors play an important role in hematopoietic stem cell transplantation outcome for hematologic and solid tumors. Incorporation of NK receptor genotyping in donor selection algorithms may benefit recipients of both HLA-matched and -mismatched allografts.