GAL-ALPHA(1,3)GAL IS THE MAJOR XENOEPITOPE EXPRESSED ON PIG ENDOTHELIAL, CELLS RECOGNIZED BY NATURALLY-OCCURRING CYTOTOXIC HUMAN-ANTIBODIES

Hyperacute rejection, mediated by natural antibody, is the major barri er to xenotransplantation. The studies reported herein were aimed at e valuating antibody-mediated cytotoxicity and the role of the Gal alpha (1,3) Gal epitope, which we had previously demonstrated was the major epitope of pig cells detected by naturally occurring human antibodies. Also, we had shown that this epitope could be induced in nonexpressin g cells by the transfection of a cDNA clone encoding alpha(1,3)galacto syl transferase, the enzyme that produces this epitope. The importance of the Gal alpha(1,3)Gal epitope was supported by (1) sugar inhibitio n studies; (2) complete absorption of cytotoxic antibodies by melibios e-sepharose columns; and (3) the ability of normal human serum to lyse COS cells after transfection with a cDNA clone encoding alpha(1,3)gal actosyl transferase. These findings strongly suggest that the majority of cytotoxic human antibodies that would recognize a xenogeneic graft are directed to theGal alpha(1,3)Gal epitope.