Human natural anti-alpha-galactosyl IgG. II. The specific recognition of alpha (1----3)-linked galactose residues.

Abstract

A natural IgG antibody (anti-Gal) with alpha-galactosyl binding specificity has been found in large amounts (0.5 - 1.0% of serum IgG) in all individuals tested. It has been purified by affinity chromatography on a column of melibiose-Sepharose. In addition to its affinity for normal and pathological senescent human red cells, the antibody readily interacts with rabbit red blood cell (RRBC) glycolipids with alpha-galactosyl terminal residues. Two types (glycosidic linkages of 1----3 vs. 1----4) of rabbit red cells glycolipids with terminal alpha-galactosyl residues were tested for antibody binding. The antibody specifically bound to glycolipids with Gal alpha 1----3 terminal residues, and treatment of these glycolipids with alpha-galactosidase abolished binding. Hemagglutination inhibition studies with oligosaccharides of known structure also showed that the antibody binds specifically to glycoconjugates with an alpha 1----3 terminal galactose residue. Anti-Gal did not bind to a human B-active glycolipid, indicating that fucose-linked alpha 1----2 to the penultimate galactose prevents anti-Gal binding. The anti-Gal specificity for RRBC glycolipids also paralleled that of the alpha-galactosyl-specific Bandeiraea simplicifolia lectin. The possible reasons for the occurrence of this unique antibody in human serum are discussed.

Role for CD47-SIRPα signaling in xenograft rejection by macrophages

“…Humans lack a functional ␣1,3-galactosyltransferase (GalT) gene, and therefore do not express Gal␣1,3Gal␤1,4GlcNAc (Gal) carbohydrate residues, and produce abundant natural antibodies (Abs) to the Gal epitope (3). These anti-Gal Abs are a major barrier to xenotransplantation of pig organs into humans, because hyperacute rejection and acute humoral rejection are initiated by their binding to Gal determinants that are ubiquitously present on porcine cells.…”

In vivo targeting of vaccinating tumor cells to antigen-presenting cells by a gene therapy method with adenovirus containing the α1,3galactosyltransferase gene

“…30 Anti-Gal interacts specifically with the a-gal epitope (Gala1-3Galb1-4GlcNAc-R), a carbohydrate epitope abundantly produced on glycoproteins and glycolipids of non-primate mammals and New World monkeys by the glycosylation enzyme a1,3galactosyl-transferase (a1,3GT). [31][32][33][34] We and others found that the a-gal epitope is absent, however, in Old World monkeys, apes and humans, because of evolutionary inactivation of the a1,3GT gene in ancestral Old World primates. [34][35][36][37] As an outcome of these evolutionary differences, anti-Gal functions in vivo as a major barrier for xenotransplantation of pig organs in humans, as its binding to a-gal epitopes on pig xenograft cells induces rapid rejection of the graft.…”

Extracellular Matrix as an Inductive Scaffold for Functional Tissue Reconstruction

“…These molecules are well characterized for their ability to promote an inflammatory or rejection type response. [189][190][191] ECM scaffold materials containing large amounts of cellular content following decellularization have been demonstrated to promote a more inflammatory, M1 type, response and result in scar tissue deposition rather than constructive remodeling. 73 Although the degree of inflammatory response appears to be linked to the quantity of cellular content, an exact threshold beyond which the constructive remodeling response is affected is unknown.…”