Prevention of Allogeneic Bone Marrow Graft Rejection by H-2 Transgene in Donor Mice

Rejection of bone marrow grafts in irradiated mice is mediated by natural killer (NK) cells and is controlled by genes linked to the major histocompatibility complex (MHC). It has, however, not been possible to identify the genes or their products. An MHC class I (D$^{\text{d}}$) transgene introduced in C57BL donors prevented the rejection of their bone marrow by NK cells in irradiated allogeneic and F$_{1}$ hybrid mice expressing the D$^{\text{d}}$ gene. Conversely, H-2D$^{\text{d}}$ transgenic C57BL recipients acquired the ability to reject bone marrow from C57BL donors but not from H-2D$^{\text{d}}$ transgenic C57BL donors. These results provide formal evidence that NK cells are part of a system capable of rejecting cells because they lack normal genes of the host type, in contrast to T cells, which recognize cells that contain abnormal or novel sequences of non-host type.