Role of NK cells in allorecognition

Missing self

Flash movie

Natural killer (NK) cells are lymphocytes of the innate immune system that kill virus infected cells and certain tumor cells without the need for prior immunization. NK cells can be activated by cytokines or when their activating receptors recognize particular ligands on virus infected cells. Uninfected host cells are protected because NK cells possess receptors for self molecules that inhibit their activation. The ligands that inhibit NK cell activation are class I itself or class I-like molecules. Killer Cell Immunoglobuline like Receptors (KIR) are an example of inhibitory receptors of NK-cells. Because NK cells already have an inherent anti-tumor activity, their alloreactivity against allogeneic leukemia cells (GvL) may be stronger that against allogeneic normal cells. If true, such cells would be the ideal effector cells to eradicate residual leukemic cells because they would have a GvL effect without attacking the normal tissues and causing a GvH.

PARHAM'S VIEW

NK alloreaction

Cell Immunoglobulin-like (KIR)-receptor specific for HLA-Cw3 will attack a cell that does not express this allele (missing self). The NK cells of a given individual express at least one inhibitory receptor recognizing one of its own HLA-alleles. However, when in transplantation the donor and recipient are HLA-mismatched, NK cells may encounter cells that do not express the HLA-allele that they are inhibited by. This NK cell is an alloreactive NK cell because it is activated by the cells of the patient and not by the cells of the donor. The nature of NK-alloreactivity might be different from the alloreactivity