Target cell susceptibility to lysis by human natural killer cells is augmented by alpha(1,3)-galactosyltransferase and reduced by alpha(1,2)-fucosyltransferase

Susceptibility of porcine endothelial cells to human natural killer (NK) ce ll lysis was found to reflect surface expression of ligands containing Gal alpha(1,3)GlcNAc, the principal antigen on porcine endothelium recognized b y xenoreactive human antibodies. Genetically modifying expression of this e pitope on porcine endothelium by transfection with the alpha(1,2)-fucosyltr ansferase gene reduced susceptibility to human NK lysis, These results indi cate that surface carbohydrate remodeling profoundly affects target cell su sceptibility to NK lysis, and suggest that successful transgenic strategies to limit xenograft rejection by NK cells and xenoreactive antibodies will need to incorporate carbohydrate remodeling.