MONOMORPHIC AND POLYMORPHIC CARBOHYDRATE ANTIGENS ON PIG-TISSUES - IMPLICATIONS FOR ORGAN XENOTRANSPLANTATION IN THE PIG-TO-HUMAN MODEL

The existence of the alphaGal epitope in 137 pigs belonging to 23 diff erent breeds suggests that this antigen is either monomorphic or occur s at a high incidence in the porcine species. Its histological locatio n at the surface of pig vascular endothelial cells makes it a target f or human natural anti-alphaGal antibodies and complement, which may be responsible for the hyperacute vascular rejection of transplanted pig organs. The precursor carbohydrate chain (N-acetyllactosamine) and Ne uAc-substituted epitopes are also exposed at the surface of pig vascul ar endothelium and were found in all pigs in this study. However, huma ns also have these two epitopes on vascular endothelium and, consequen tly, have not made natural antibodies against these carbohydrate antig ens. Therefore, these two pig epitopes cannot be the main target of th e hyperacute vascular rejection process. Three pig phenotypes - A + (5 1%), A:H + (38%), and A - H - I + (11%) were identified among 37 Large -white pigs by the presence of polymorphic A, H, and I carbohydrate an tigens on the brush border of the surface epithelium of small intestin e. These antigens were also present in other exocrine secretions but w ere not detected on vascular endothelium of the same pigs, suggesting that they are not involved in the hyperacute vascular rejection, altho ugh the pig A tissue antigen can induce an immune response in 0 or B b lood group recipients. Once the problem of the initial hyperacute vasc ular rejection directed against the alphaGal epitope is overcome, typi ng donor pigs for A, H, and I, as well as for the protein swine leukoc yte antigens (SLA) and other pig antigens, may help in elucidating ant igens involved in acute or chronic xenograft rejection.