Natural killer cell target

Natural Killer (NK) cells are innate lymphoid cells that specialize in the surveillance and elimination of cells that have undergone malignant transformation or viral infection. These target cells are characterized by two primary signals: the loss of Major Histocompatibility Complex (MHC) class I molecules (the 'missing self' hypothesis) and the upregulation of stress-induced ligands such as MICA, MICB, and ULBPs (the 'induced self' signal) (Lanier, 2005). MHC class I molecules normally provide inhibitory signals to NK cells via Killer-cell Immunoglobulin-like Receptors (KIRs) or NKG2A, preventing the destruction of healthy 'self' cells. When these inhibitory signals are lost or overridden by activating signals from ligands binding to receptors like NKG2D, the NK cell releases cytotoxic granules containing perforin and granzymes to induce apoptosis in the target cell (Vivier et al., 2011). Therapeutic interventions aim to exploit this mechanism by using monoclonal antibodies to block inhibitory receptors, such as Monalizumab (targeting NKG2A) and Lirilumab (targeting KIRs), or by using cytokines like IL-15 to enhance NK cell proliferation and effector function (André et al., 2018; Waldmann, 2006).

Other names

NK cell targetsMHC-I deficient cellsNKG2D ligand-expressing cellsMissing-self cellsInduced-self cells

Enhancement of Natural Killer (NK) cell-mediated cytotoxicity through the blockade of inhibitory receptors or activation of stimulatory receptors.