POSITIVE AND NEGATIVE MHC CLASS-I RECOGNITION BY RAT NK CELLS

The prompt rejection of transplanted allogeneic lymphocytes by rat NK cells in non sensitized recipients (allogeneic lymphocyte cytotoxicity or ALC) is determined by MHC genes as well as by genes located in the NK complex. The same genetic control is found when NK alloreactivity is measured by an in vitro assay, and we have employed this assay to d elineate the specificity of NK cells for the MHC. The MHC of the rat, RT1, contains class I genes situated on either side of the class II/cl ass III region. The majority of these class I genes are located in the RT1.C region and expressed class I products usually behave as non-cla ssical (class Ib) molecules. They do not serve as restriction elements for the vast majority of conventional alpha/beta T-cells, in contrast to those class I molecules encoded by one or more loci in the classic al (class Ia) region, RT1.A. However, NK cells appear to recognize the products of either class I region. Immunogenetic studies suggest that NK cells are inhibited by RT1.A molecules, whereas RT1.C region molec ules may have a dual role in regulating NK cytolytic activity i.e. the y either inhibit or activate natural killing. Based on these premises, a model is proposed in which identification of a target as self or no n-self depends on different receptors for class I in single NK cells, interpreting coincident positive and negative signals from the various target class I molecules. The putative role of peptides presented by class I, the biological implications, and the evolution of the NK rece ptors and their ligands are discussed.