Cells of nonprimate mammals express an abundance of the carbohydrate structure Galal-3Gal~ l-4GlcNAc-R (termed the a-galactosyl epitope). The natural anti-Gal antibody, which interacts specifically with ot-galactosyl epitopes, is present in high concentrations in all humans. Here, Uri Galili argues that the interaction between anti-Gal in the serum and a-galactosyl epitopes on cells of nonprimate grafts may act as an immunological barrier which prevents xenotransplantation.

The development of potent immunosuppressive drugs in the recent two decades has facilitated the success of allogeneic transplantation of human organs such as kidney, heart and liver. However, donor organ shortages limit the number of patients that can be treated. This has increased the interest in the possible use of xenogeneic organs for transplantation in human& 3. The use of primate donors is restricted by their number in captivity and by concerns for animal rights, prompting intensive research in the possible use of nonprimate mammals (in particular pigs) as xenograft donors 1-3. Such xenografts, which have been termed'discordant xenografts' because of their evolutionary distance from humans or primates 4, usuaily undergo hyperacute rejection in primate recipients. Hyperacute rejection