[Alpha]-Gal and Anti-Gal [Alpha] 1,3-Galactosyltransferase, [Alpha]-Gal Epitopes, and the Natural Anti-Gal Antibody Subcellular Biochemistry - Subcellular Biochemistry

This is an interdisciplinary work which assembles the wide spectrum of information on the basic and clinical aspects of the natural anti-Gal antibody, the a-gal epitope and the enzyme producing it, a-1,3-galactosyltransferase.;Anti-Gal is the most abundant antibody in humans, apes and Old World monkeys (monkeys of Asia and Africa). It binds specifically to the a-gal epitope (Gala1-3Galb1-4GlcNAc-R) on glycoproteins and glycolipids. Humans, apes and Old World monkeys lack a-gal epitopes. In contrast, the a-gal epitope is produced in large amounts on cells of nonprimate mammals, prosimians and New World monkeys (monkeys of South America), by the glycosylation enzyme a-1,3-galactosyltransferase. This differential distribution of the a-gal epitope and anti-Gal in mammals is the result of an evolutionary selective process which led to the inactivation of a-1,3-galactosyltransferase in ancestral Old World primates. A direct outcome of this event is the present rejection of xenografts such as pig organs in humans and monkeys because of the binding of human anti-Gal to a-gal epitopes on pig cells.;The various chapters were contributed by researchers studying basic and clinically related aspects of this area. It aims to provide comprehensive and updated information on this antigen/antibody system, which at present is the major obstacle in xenotransplantation, and on some of the genetic engineering approaches developed for overcoming this obstacle. In addition, it describes the significance of anti-Gal and a-gal epitopes in some parasitic, bacterial and viral infections, as well as in the pathogenesis of autoimmune diseases such as Graves' disease. Finally, it describes novel approaches for exploiting the natural anti-Gal antibody for increasing immunogenicity of cancer and viral vaccines in humans.;The contributions are edited and partly written by Dr Uri Galili who originally discovered anti-Gal and the unique evolution of a-1,3-galactosyltransferase, and by Dr Jose-Luis Avila who has been studying anti-Gal significance in Chagas' disease and in Leishmania infections.;This work covers the main areas of research on a-1,3galactosyltransferase, its product the a-gal epitope (Gala1-3Galb1-4GlcNAc-R) and the natural anti-Gal antiboy that interacts with this epitople. It includes chapters on: The evolution of a-1,3 galactosyltransferase in mammals; the structure of the a-1,3galactosyltransferase gene; the structure function relationship of the a 1,3galactosyltransferase enzyme; the molecular characteristics of a-gal epitopes on glycolipids and glycoproteins and methods for its detection; the natural anti-Gal antibody and its significance in xenotransplantation; attempts to prevent xenograft rejection by elimination of a-1,3galactosyltransferase gene, and by modulating a-gal epitope expression and anti-Gal activity; significance of anti-Gal and a-gal epitopes in viral, bacterial and protozoal infections; and the possible clinical exploitation of anti-Gal for the enhancement of cancer and viral vaccine immunogenicity.