MHC class Ia molecules alone control NK-mediated bone marrow graft rejection

Mice with functionally deleted genes encoding MHC class I heavy (H-2K(b), H -2D(b)) and light (beta 2-microglobulin) chains were used in bone marrow ce ll transfer experiments to study the role of class la and Ib molecules in N K cell function. Absence of H-2K(b) and absence of H-2D(b) on bone marrow c ells resulted in complete and in almost complete NK-mediated rejection, res pectively. Absence of either H-2 class Ib (at least when expressed in H-2 c lass Ia-deficient mice) or cell surface class la free heavy chains did not result in bone marrow rejection. Thus, in C57BL/6 adult mice, the inactivat ion of NK cells required for bone marrow cell engraftment relies entirely u pon-H-2 class la molecules. These results imply the existence of an inhibit ory receptor which recognizes either directly or indirectly H-2Db molecules and further suggest that in C57BL/6 mice the NK cells which do not express a H-2K(b) specific inhibitory receptor necessarily express an H-2D(b)-spec ific one.