INTRODUCTION OF ALPHA(1,2)-FUCOSYL-TRANSFERASE AND ITS EFFECT ON ALPHA-GAL EPITOPES IN TRANSGENIC PIG

Hyperacute rejection (from pig to human) is thought to result from act ivation of complement initiated by the binding of host natural antibod ies to alpha-galactosyl (alpha-Gal) epitopes of donor endothelial cell s. However, alpha-Gal epitope shares a common precursor with H antigen in humans. This means that H antigens as well as alpha-Gal epitopes a re synthesized in a competitive manner by different enzymes. We though t that it would be possible to convert alpha-Gal epitopes into H antig ens by introducing cDNA of alpha(1,2)-fucosyltransferase (alpha 1-2FT) into porcine cells, and so, pig embryos were microinjected with alpha 1-2FT cDNA. Transgenic pigs that carried alpha 1-2FT were thus establ ished. Cytotoxicity of fibrocytes derived from skin of transgenic pig was measured by Cr-51 release assay, which showed that H antigen-expre ssing cells were significantly resistant to a challenge with human ser a. These experiments indicate that our method provides a new strategy which contributes to a successful discordant xenotransplantation.