Histocompatibility antigens and natural killer susceptibility

The central question of the nature of the structure(s) involved in the recognition of targets by natural killer (NK) cells remains unresolved. Although NK-mediated cytotoxicity is not MHC-restricted, it has been suggested that these cells could recognize the targets more effectively in the absence of MHC class I antigens. In this paper we review the contradictory results obtained when studying the NK susceptibility of cell lines which constitutively express different levels of MHC antigens, or which have been induced to express MHC antigens by gene transfection or gamma-interferon treatment. Taken together, the results indicate that MHC antigens play a differential role in NK lysis depending on the nature of the target cells used; MHC class I antigens play a role in the NK resistance of cells from a hematopoietic lineage, but this does not extend to cells from other origins. The data reviewed also support the hypothesis that MHC class I antigens induced NK resistance by interfering with target structures, and that multiple NK molecules are involved in NK-mediated lysis as part of a possible advanced recognition system.