REDUCTION OF THE MAJOR SWINE XENOANTIGEN, THE ALPHA-GALACTOSYL EPITOPE BY TRANSFECTION OF THE ALPHA-2,3-SIALYLTRANSFERASE GENE

alpha 2,3-Sialyltransferase represents a putative enzyme that reduces the Gal alpha 1-3Gal beta 1-4GlcNAc-R (the alpha-galactosyl epitope) b y intracellular competition with alpha 1,3-galactosyltransferase for a common acceptor substrate. This study demonstrates that the overexpre ssion of the alpha 2,3-sialyltransferase gene suppresses the antigenic ity of swine endothelial cells to human natural antibodies by 77% rela tive to control cells and by 30% relative to cells transfected with al pha 1,2-fucosyltransferase, and in addition, it reduces the complement -mediated cell lysis by 75% compared with control cells and by 22% com pared with cells transfected with alpha 1,2-fucosyltransferase. The me chanism by which the alpha-galactosyl epitope was reduced was also stu died. Suppression of alpha 1,3-galactosyltransferase activity by 30-63 % was observed in the transfectants with alpha 2,3-sialyltransferase, and mRNA expression of the alpha 1,3-galactosyltransferase gene was re duced as well. The data suggest that the alpha 2,3-sialyltransferase e ffectively reduced the cy-galactosyl epitope as well as or better than the alpha 1,2-fucosyltransferase did and that the reduction of the al pha-galactosyl epitope is due not only to substrate competition but al so to an overall reduction of endogenous alpha 1,3-galactosyltransfera se enzyme activity.