MHC gene control of the natural killer system at the level of the target and the host

Natural killer (NK) cells represent an important complementary and alternative effector mechanism in cell-mediated immunity since they can recognize alterations that cannot be detected by the peptide/MHC specific T cells. NK cells can probably utilize several parallel recognition mechanisms to distinguish and eliminate aberrant cells. This article reviews studies starting from the idea that one of the NK recognition strategies is based on the ability to identify missing self MHC class I products on potential target cells. In the murine RBL-5 lymphoma system, this is supported by the NK mediated rejection, observed either after loss of MHC products in the target cell, or after introduction of a novel class I transgene in the host. 'Missing self' recognition by NK cells may be an important factor when analysing tumor MHC expression in relation to prognosis, immunoselection, cytokine-activated effector cells and immunotherapy.