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Hybrid resistance refers to the rejection of parental strain bone marrow cells by natural killer cells of mice that are F1 hybrids derived from two inbred parental strains. This pattern of rejection is not seen in solid organ transplants. Progress in understanding this exception to the laws of transplantation genetics has occurred with the recent discovery of negative signaling receptors for MHC class I molecules. In the last year the discovery of natural killer cell subsets with non-overlapping inhibitory receptors for parental class I molecules has provided an explanation for hybrid resistance. In some instances, however, positive rather than negative signaling seems to be the basis for rejection of allogeneic as well as parental marrow cell grafts.
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