Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1----3Gal epitope in primates.

Abstract

Anti-Gal is a natural antibody, which constitutes as much as 1% of circulating IgG in humans and displays a distinct specificity for the structure Gal.alpha.1 .fwdarw. 3Gal. This glycosidic structure has been found on various tissues of many nonprimate mammals. A comparative study of the occurrence of anti-Gal versus the expression of the Gal.alpha.1 .fwdarw. 3Gal epitope was performed in primates, and a distinct evolutionary pattern was observed. Whereas anti-Gal was found to be present in Old World monkeys and apes [Macaca mulatta, M. maura, M. fascicularis, M. nemestrina, M. arctoides, Papio papio and Cercopithecus diana] in titers comparable to those in humans, its corresponding antigenic epitope is abundantly expressed on erythrocytes of New World monkeys [Callithrix jacchus, Aotus trivirgatus, Saguinus mystax, Saimiri sciureus, Cebus apella, Ateles paniscus, Alouatta caraya and Lagothrix lagothricha]. Immunostaining with anti-Gal of glycolipids from New World monkey erythrocytes indicated that the molecules to which anti-Gal binds are similar to those found in rabbit and bovine erythrocytes. These findings indicate that there is an evolutionary reciprocity between New World and Old World primates in the production of the Gal.alpha.1 .fwdarw. 3Gal structure and the antibody that recognizes it. The expression of the Gal.alpha.1 .fwdarw. 3Gal epitope was evolutonarily conserved in New World monkeys, but it was suppressed in ancestral lineages of Old World primates. The suppression of this epitope was accompanied by the production of anti-Gal. The observed in vivo binding of anti-Gal to human normal senescent and some pathologic erythrocytes implies that the Gal.alpha.1 .fwdarw. 3Gal epitope is present in man in a cryptic form.