Triggering of natural killer cell mediated cytotoxicity by costimulatory molecules.

Abstract

Natural killer (NK) cell mediated cytotoxicity is affected by both triggering and inhibitory signals (see e.g., Gumperz and Parham 1995; Lanier and Philips 1996; Raulet 1996). In several models target cell major histocompatibility complex (MHC) class I molecules have been demonstrated to be able to turn off NK cells (Ljunggren and Karre 1990; Karre 1995) by delivering inhibitory signals to MHC class I binding receptors (Karlhofer et al. 1992; Yokoyama and Seaman 1993). The latter include members of the Ly-49 receptors in mouse and the killer-cell inhibitor receptors (KIR) in man (Gumperz and Parham 1995; Lanier and Philips 1996; Raulet 1996). While much attention has been focused on the role of MHC class I inhibition of NK cell mediated cytotoxicity in recent years, significantly less attention has been devoted to receptor-ligand interactions that may trigger cytotoxicity. This review discusses new insights into the ability of costimulatory molecules to trigger NK cell mediated cytotoxicity.