[Why humans and Catarrhini lack the Galalpha1-3Gal epitope, related to xenograft rejection?]

The Galalpha1-3Gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) is an oligosaccharide determinant present on the cell surface of most mammalian species with the exception of the higher primates, including Old World monkeys, apes, and humans. The synthesis of Galalpha1-3Gal epitope is catalyzed by alpha1,3-galactosyltransferase (alpha1,3GT). Inactivation of the alpha1,3GT gene in humans and the production of natural anti-Galalpha1-3Gal antibodies against the Galalpha1-3Gal epitope has resulted in the formation of a unique immunological barrier that prevents the transplantation of tissues and organs from Galalpha1-3Gal-positive animals to humans. The gene encoding a1,3-galactosyltransferase in higher primates is inactive due to point mutations and deletions leading to a change of reading frame. The human transcript of this gene consists of several splicing variants, most of which does not contain an exon encoding the catalytic domain. Thus no active protein is produced.