Natural killer cell interaction with murine allogeneic MHC class I molecules.

Class I molecules of the MHC affect target cell sensitivity to NK cell repertoire. In the mouse, absence of MHC class I molecules on target cells is associated with an increased susceptibility to NK cell-mediated lysis, while syngeneic class I molecules confer protection. In contrast to the protective role of syngeneic class I molecules, less is known about the interaction between murine NK cells and allogenic class I MHC molecules. In theory, such could either be triggering, inert, or inhibitory. To directly address the role of allogeneic class I in interaction with NK cells of the mouse, a panel of polyclonal allogeneic murine NK cells were exposed to H-2b class I positive or negative target cells, and susceptibility to lysis was assessed. For all effectors studied, regardless of H-2 haplotype or genetic background, a preferential killing of class I-deficient targets was observed. This pattern was observed in vitro with tumor as well as lymphoblast targets, and in vivo in rapid elimination studies of radiolabeled tumor cells. The results demonstrate that protection from murine NK cell-mediated lysis can be conferred by the expression of allogeneic class I molecules. No evidence for a triggering effect caused by the expression of allogeneic class I molecules was observed. The data are discussed in relation to current models on NK cell/MHC class I interactions, alloreactivity mediated by NK cells, and the role of NK cells in allogeneic graft rejection responses.