Assays for Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Reverse ADCC (Redirected Cytotoxicity) in Human Natural Killer Cells

Crosslinking of molecules involved in the recognition of target cells elicits natural killer (NK) cell cytotoxicity, inducing either release of preformed cytotoxic mediators via granule exocytosis, or (enhanced) expression of ligands for target cell membrane-associated molecules that transduce apoptotic signals, e.g., Fas Ligand (FasL) or TRAIL (reviewed in refs. 1 ,2 ). Target cell recognition by NK cells occurs via either of two ways: (1) receptors capable of binding molecules on the target cells that include, but are not limited to, adhesion molecules and the identities of which are incompletely defined (reviewed in ref. 3 ); and (2) receptors for the Fc fragment of IgG (FcγRIIIA, CD 16) (4 , reviewed in ref. 5 ). The latter bind immunecomplexed IgG and therefore target cells that, not recognized spontaneously by NK cells, are sensitized with anti-target cell antibodies (Abs) of the IgG class. The two types of cytotoxicity elicited are referred to as “spontaneous” and “Ab-dependent’ cell-mediated cytotoxicity (ADCC).