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J Biol Chem, Vol. 274, Issue 16, 10717-10722, April 16, 1999

Target Cell Susceptibility to Lysis by Human Natural Killer Cells Is Augmented by (1,3)-Galactosyltransferase and Reduced by (1,2)-Fucosyltransferase

John H. Artrip, Pawel Kwiatkowski, Robert E. Michler, Shu-Feng Wang, Sorina Tugulea, Jan Ankersmit, Larisa Chisholm^¶, Ian F. C. McKenzie^¶, Mauro S. Sandrin^¶, and Silviu Itescu

From the  College of Physicians and Surgeons, Columbia University, New York, New York 10032 and ^¶ Austin Research Institute, Heidelberg, Victoria 3084, Australia

Susceptibility of porcine endothelial cells to human natural killer (NK) cell lysis was found to reflect surface expression of ligands containing Gal (1,3)GlcNAc, the principal antigen on porcine endothelium recognized by xenoreactive human antibodies. Genetically modifying expression of this epitope on porcine endothelium by transfection with the (1,2)-fucosyltransferase gene reduced susceptibility to human NK lysis. These results indicate that surface carbohydrate remodeling profoundly affects target cell susceptibility 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.

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