title: Recent investigations into pig antigen and anti-pig antibody expression.
abstract: Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.
authors: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA; Institute of Cardiovascular Science, University College London, London WC1E 6JF, UK. Electronic address: guerard.byrne@ucl.ac.uk.
authors: Guerard W
authors: GW
authors: Byrne
authors: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA; Institute of Cardiovascular Science, University College London, London WC1E 6JF, UK.
authors: Christopher G A
authors: CGA
authors: McGregor
authors: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
authors: Michael E
authors: ME
authors: Breimer
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000276:immunology; D000906:Antibodies / Q000378:metabolism*; D004187:Disaccharides / Q000276:immunology / Q000378:metabolism; D005818:Genetic Engineering / Q000379:methods; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology; D011323:Primates / Q000276:immunology; D013552:Swine / Q000235:genetics / Q000276:immunology*; D014183:Transplantation, Heterologous; D019737:Transplants / Q000276:immunology*
chemical_list: D000906:Antibodies; D004187:Disaccharides; D011134:Polysaccharides; C055075:galactosyl-(1-3)galactose; D019158:N-Acetylneuraminic Acid
keywords: Antibody; Antigen; Non-Gal; Xenotransplantation