Glycan Antigens of Pig Interfering with Xenotransplantation: Three Immune Responses from the Glycans

Human beings commonly understand carbohydrates or glycans only as a source of bioenergy. Because the proteins are biosynthesized in eukaryotic endoplasmic reticulum (ER) and Golgi apparatus, the N/O-glycans not only stabilize the protein synthesis process in ER and Golgi apparatus but also relates to cell-to-cell communication in cell membranes. Furthermore, glycans are also important to immune responses due to their interaction with lectins. All animals synthesize their unique glycans from each species and present them to the cell membrane. For example, human beings synthesize oligosaccharide from a dolichol (Dol) structure in the rough ER and do N-linked glycosylation. Then, O-glycan glycosylation take places in the Golgi apparatus, adding and removing various saccharides including galactose (Gal), mannose (Man), and N-acetylglucosamine (GlcNAc). Created glycans confer species specificity of each individual and play major antigen roles in xenotransplantation. Other types of glycans in the graft cell cause a more rapid immune response than protein antigens, causing the xenotransplantation to fail. In this regard, consider the glycans of pigs, which is the most suitable animal for xenotransplantation. α1, 3-Gal, Neu5Gc, and Sd(a), which are expressed in pigs but not in humans, cause various immune responses in humans to fail in xenotransplantation. Also, the major MHC or HLA should be considered crucial for transplantation. Their interspecies differences also act as barriers of xenotransplantation. If they can be removed from these interactions, it can be possible to success the xenotransplantation.