The sweets standing at the borderline between allo- and xenotransplantation

Animal cells are densely covered with glycoconjugates, such as N-glycan, O-glycan, and glycosphingolipids, which are important for various biological and immunological events at the cell surface and in the extracellular matrix. Endothelial α-Gal carbohydrate epitopes (Galα3Gal-R) expressed on porcine tissue or cell surfaces are such glycoconjugates and directly mediate hyperacute immunological rejection in pig-to-human xenotransplantation. Although researchers have been able to develop α1,3-galactosyltransferase (GalT) gene knockout (KO) pigs, there remain unclarified non-Gal antigens that prevent xenotransplantation. Based on our expertise in the structural analysis of xenoantigenic carbohydrates, we describe the immunologically significant non-human carbohydrate antigens, including α-Gal antigens, analyzed as part of efforts to assess the antigens responsible for hyperacute immunological rejection in pig-to-human xenotransplantation. The importance of studying human, pig, and GalT-KO pig glycoprofiles, and of developing adequate pig-to-human glycan databases, is also discussed.