Preformed and elicited antibodies to pig antigens in nonhuman primates and humans

Antibodies against pig antigens mediate much of the pig xenograft rejection process in humans and in evolutionarily related primates. The main, and possibly the only, natural antibody that induces rejection of pig xenografts is anti-Gal, which interacts with α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) on pig cells. However, in xenograft recipients there are two types of elicited (ie, induced) anti-pig antibodies that are detrimental to the xenograft: 1) elicited anti-Gal IgG, which displays approximately 100-fold increase in activity in comparison with the natural anti-Gal, and 2) anti–non-gal antibodies against a large number of immunogenic pig proteins. If complement activation is prevented, these antibodies destroy xenograft cells, primarily via the antibody-dependent cell-mediated cytotoxicity mechanism. Progress in xenotransplantation requires the development of novel methods for preventing the production of these natural and elicited antibodies.