Play it in E or G: utilization of HLA-E and -G in xenotransplantation

Human NK cell-mediated graft rejection is likely to be one of several biological obstacles to routine pig-to-human xenotransplantation. Abrogating NK cell activation by either elimination of activating ligands on porcine cells or expression of molecules serving as ligands for NK cell inhibitory receptors, or both, could overcome this hurdle. HLA-E and -G exhibit very limited polymorphism and are ligands for NK cell inhibitory receptors. This review summarizes successes and limitations of their use in xenotransplantation as inferred from ex vivo analyses of NK cell activity, highlights potential effects they may have on T-cell responses, and considers prospects of preclinical trials and potential outcomes.