Natural killer (NK) cells can defend an organism against a variety of threats, probably using several different strategies to discriminate between normal and~ berrant cells. According to the'missing self" hypothesis, one function of NK cells is to recognize and eliminate cells that fail to express self major histocompatibility complex (MHC) class I molecules. In this article Hans-Gustaf Ljunggren and Klas K6rre review in vivo stbdies with H-2-deficient targets that support this hypothesis. In vitro stlldies, some of which have given conflicting results, are interpreted wlthin a multiple choice model for NK cell recognition. The authors derive testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction.

T cells recognize nonself antigens in association with MHC molecules, for example on transformed or virus-infected cells-3. Such is the sensitivity of recognition that single amino acid substitutions in an MHC class I molecule or a peptide antigen can be sufficient to create a foreign determinant detected by cytotoxic T cells (CTL) 4.5. NK cells can also discriminate between aberrant~ nd normal cells. They can reject transformed, virus-infected and nonsyngeneic hemopoietic cells and thereby protect an animal from death 6-9. However, it has been difficult to define minimal changes that determine whether an NK cell will lyse or spare an aberrant cell from lysis.