A ligand for the murine NK activation receptor LY-49D: Activation of tolerized NK cells from β₂-microglobulin deficient mice

Mouse NK cells express inhibitory NK receptors that recognize target cell MHC class I molecules and activation receptors that are less well defined. The Ly-49D activation receptor on C57BL/6 NK cells recognizes Chinese hamster ovary cells and triggers natural killing. In this study, we demonstrate that a Chinese hamster classical MHC class I molecule is the ligand for Ly-49D in a reporter gene assay system as well as in NK cell killing assays. Ly-49D recognizes the Chinese hamster class I molecule better when it is expressed with Chinese hamster β₂- microglobulin (β₂m) than murine β₂m. However, it is still controversial that Ly-49D recognizes H-2D^d, as we were unable to demonstrate the specificity previously reported. Using this one ligand-one receptor recognition system, function of an NK activation receptor was, for the first time, investigated in NK cells that are tolerized in β₂m-deficient mice. Surprisingly, Ly-49D-killing activity against ligand -expressing targets was observed with β₂m-deficient mouse NK cells, albeit reduced, even though "tolerized" function of Ly-49D was expected. These results indicate that Ly-49D specifically recognizes the Chinese hamster MHC class I molecule associated with Chinese hamster β₂m, and indicate that the Ly-49D NK cell activation receptor is not tolerized in β₂m deficiency.