Stimulatory Receptors in NK and T Cells

Abstract

Although it has long been known that natural killer (NK) cells lyse certain tumor or virally infected cells (Herberman et al. 1979; Kiessling et al. 1979; Trinchieri 1989), the mechanism(s) by which they discriminate between these target cells and normal cells remained mysterious. More recently, important progress both in mice and in humans has allowed at least in part the clarification of the molecular mechanisms involved in NK cell function and in their ability to identify and lyse potentially dangerous target cells (Yokoyama and Seaman 1993; Moretta L. et al. 1992, 1994; Moretta A. et al. 1996). An inverse correlation has been established between the expression of surface MHC class I molecules on potential target cells and their susceptibility to NK cell mediated lysis (Ljunggren and Kärre 1990; Kärre 1992). This led to the hypothesis that the surface expression of MHC molecules in some way protects cells from NK cell mediated attack. Cells in which MHC molecules are not expressed (as may occur in tumor or virus-infected cells) are susceptible to NK cells (Ljunggren and Kärre 1985). Thus NK cells may play a unique role in immune defenses by selectively removing cells that have lost the ability to express MHC class I molecules.