Clinical relevance of KIRs in hematopoietic stem cell transplantation

Natural Killer cells (NK cells) represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitived target cells could be mediated independently of antigen stimulation, and unlike cytotoxic T-lymphocytes, they do not require peptide presentation by the major histocompatibility complex (MHC) molecules. NK cell cytotoxic activity is controlled by considerable number of cell surface Killer cell Immunoglobulin like Receptors (KIRs), which can exist in both inhibitory and activating isoforms. The inhibitory KIRs are mostly specific for HLA class I ligands and I HLA class like molecules, while the specificity of activating receptors is regarded to lectine-like superfamily. The role of NK cells in allogeneic haematopoietic stem cell transplantation (HSCT): NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT By selecting donors mismatched for relevant HLA ligands in the context of recipients KIR genotype, multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD) through selective killing of recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL) effect through destruction of residual host tumor cells.