Glycoantigen and Xenotransplantation

Abstract

The α-Gal epitope (Gal α1-3Galβ1-4 GlcNAc-R), which is biosynthesized by the action of α1,3-galactosyltransferase (α1,3GT), is closely associated with hyperacute rejection (HAR) in pig to human xenotransplantation. On the other hand, the Hanganutziu-Deicher (H-D) epitope, which is produced by cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) and contains N-glycolylneuraminic acid (NeuGc), and other currently unknown non-Gal epitopes are also factors in the xenotransplantation field. At present, α1,3GT/CMAH knockout pigs have already been produced. A variety of strategies have been pursued to reduce or eliminate the α-Gal epitope from pig tissues. In addition to knocking out α1,3GT/CMAH by nuclear transplantation techniques from the targeted somatic cells, other strategies, such as enzyme competition of α1,3GT with α1,2-fucosyltransferase (α1,2FT), control of sugar processing by β-D-mannoside β1,4-N-acetylglucosaminyltransferase III (GnT-III), and digesting α-Gal epitopes by cleaving the β-galactosidic linkage, have provided very interesting insights into the downregulation of the xenogeneic epitope. Some of the above strategies continue to be downregulating the non-α-Gal epitopes in transgenic animals after α1,3GT and CMAH are eliminated. In addition, porcine endogenous retrovirus (PERV) contains a ligand with an N-linked sugar. Modification of the glycosylation pattern of the PERV ligand appears to be associated with regulating PERV infectivity.