In this issue of Blood, Barao and colleagues describe repopulation of Ly49G2 single-positive NK cells after congenic hematopoietic stem cell transplantation (HSCT) that appear fully functional, having tumor cytolytic capacity despite recipients lacking MHC molecules thought necessary to license them.Natural killer (NK) cells are innate lym-phocytes capable of killing tumors and virus-infected cells. Their function is regulated through a variety of different receptors. In humans, the largest group of receptors belongs to the killer Immunoglobulin-like family, or KIRs. Although structurally different from KIRs, mice possess Ly49 receptors that share similar functional characteristics; both" KIRs and Ly49 receptors are composed of members possessing inhibitory or activating properties that regulate the function of the NK cell on binding its cognate MHC class I ligand. Although cell subsets lacking inhibitory receptors for self-MHC have been observed in both man and mouse, in vitro studies have shown that these potentially auto-reactive NK-cell populations are in most cases rryporesponsive.
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