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It has been 15 years since the first report on the isolation of anti-Gal from human serum and the demonstration that this antibody is the most prevalent antibody in humans (Galili et al. , ]. Exp. Med. 160: 1519, 1984). Subsequent interdisciplinary studies in immunology, carbohydrate biochemistry, molecular biology, and evo lution demonstrated the highly restricted specificity of anti-Gal for the carbohy drate epitope Gal al-3Galpl-4GIcNAc-R, (termed here the a-gal epitope), the unprecedented evolutionary pattern of distribution of a-gal and anti-Gal in mam mals, and explained the evolution of this antigen and antibody by analysis of the a 1 ,3galactosyltransferase gene, the gene that encodes the enzyme that synthesizes the a-gal epitope. These studies have suggested that a major selection process that occurred in the course of evolution of ancestral Old World primates resulted in the inactivation of the a1 ,3galactosyltransferase gene and the subsequent appearance of anti-Gal in these primates. Other studies in immunoparasitology have demon strated the possible physiologic significance of anti-Gal in protection against cer tain parasitic infections. Major scientific attention was focused on a-gal and anti-Gal with the real ization in the early nineties that the interaction between this antigen and antibody is the major obstacle to xenotransplantation. The success of immunosuppressive drugs, in the last two decades of the 20th century, in preventing allograft rejection, has raised hopes for cure in many patients in need of organ transplant. Because of limited supply of allografts, only 20% of patients receive the needed organ.
List of contents
1 Evolution of ?l,3Galactosyltransferase and of the ?-Gal Epitope.- 2 The ?1,3-Galactosyltransferase Gene.- 3 Structure Function Studies of a New World Monkey ?1,3Galactosyltransferase: Analysis of Alternative Splicing and Expression in Baculovirus System.- 4 The Natural Anti-Gal Antibody.- 5 ?-Gal Epitopes in Animal Tissue Glycoproteins and Glycolipids.- 6 The Griffonia simplicifolia I - B4 Isolectin: A Probe for ?-D- Galactosyl End Groups.- 7 ?-Gal Epitopes on Viral Glycoproteins.- 8 ?-Galactosyl-Bearing Epitopes as Potent Immunogens in Chagas' Disease and Leishmaniasis.- 9 Enterotoxin A of Clostridium difficile and ?-Gal Epitopes.- 10 Anti-Gal, ?-Gal Epitopes, and Xenotransplantation.- 11 Generation of ?1,3Galactosyltransferase Deficient Mice.- 12 Anti-Xenograft Immune Responses in ?1,3-Galactosyltransferase Knock-Out Mice.- 13 Modulation of ?Gal Epitope Expression on Porcine Cells.- 14 Graves' Disease as a Model for Anti-Gal Involvement in Autoimmune Diseases.- 15 Enhancement of Autologous Tumor Vaccine Immunogenicity by Anti-Gal.
Summary
Anti-Gal is the most abundant antibody in humans, apes and Old World monkeys (monkeys of Asia and Africa). This title assembles the spectrum of information on the basic and clinical aspects of the natural anti-Gal antibody, the alpha-gal epitope and the enzyme producing it, alpha-1,3-galactosyltransferase.
