Strahan K, Preece A, Gustafsson K
Division of Cell & Molecular Biology, Institute of Child Health, University of London, 30 Guilford St., London WC1N 1EH, UK.
Front Biosci. 1996 Jul 1;1:e34-41. doi: 10.2741/a141.
Terminal carbohydrate residues of glycolipids and glycoproteins display polymorphism among as well as within various species. With the exception of Old World monkeys, great apes and man, the Gala1,3Gal structure is widely expressed in all mammals examined so far. The lack of expression of the glycosyltransferase responsible for the synthesis of Gala1,3Gal leads to the production of high titers of natural antibodies (NAb) against the Gala1,3Gal of other species. The inactivation of this gene occurred during early evolution of primates. Neutralization of viruses (e.g. retroviruses) carrying the epitope, by the pre-formed human NAb, indicates one possible evolutionary reason for the polymorphism of terminal carbohydrates among as well as within species. It has been shown that this epitope constitutes the major target, on pig endothelial cells (EC), for the pre-formed human NAb resulting in a hyperacute rejection (HAR) response. This currently makes transplantation of e.g. pig organs to humans impossible. Efforts are currently underway to prevent or to eradicate the expression of this epitope in transgenic pigs. Such pigs are likely to display a greatly increased resistance to the HAR.
糖脂和糖蛋白的末端碳水化合物残基在不同物种之间以及同一物种内部均表现出多态性。除了旧世界猴、大猩猩和人类外，α-Gal1,3Gal结构在迄今为止检测的所有哺乳动物中广泛表达。负责合成α-Gal1,3Gal的糖基转移酶表达缺失，导致产生针对其他物种α-Gal1,3Gal的高滴度天然抗体（NAb）。该基因的失活发生在灵长类动物的早期进化过程中。预先形成的人类NAb对携带该表位的病毒（如逆转录病毒）的中和作用，表明了物种间以及物种内末端碳水化合物多态性的一种可能的进化原因。研究表明，该表位是猪内皮细胞（EC）上预先形成的人类NAb的主要靶点，可导致超急性排斥（HAR）反应。目前，这使得例如将猪器官移植给人类成为不可能。目前正在努力防止或消除转基因猪中该表位的表达。这类猪可能对HAR表现出极大的抗性增强。
