Structural biology of carbohydrate xenoantigens

Abstract

Transplantation of organs across species (xenotransplantation) is being considered to overcome the shortage of human donor organs. However, unmodified pig organs undergo an antibody-mediated hyperacute rejection that is brought about by the presence of natural antibodies to Gala(1,3)Gal, which is the major carbohydrate xenoantigen. Genetic modification of pig organs to remove most of the Gala(1,3)Gal epitopes has been achieved, but the human immune system may still recognize residual lipid-linked Gala(1,3) Gal carbohydrates, new (cryptic) carbohydrates or additional non-Gala(1,3) Gal carbohydrate xenoantigens. The structural basis for lectin and antibody recognition of Gala(1,3)Gal carbohydrates is starting to be understood and is discussed in this review. Antibody binding to Gala(1,3)Gal carbohydrates is predicted to primarily involve end-on insertion of the terminal aGal residue, but it is possible that groove-type binding can occur, as for some lectins. It is likely that similar antibody and lectin recognition will occur with other non-Gala(1,3)Gal xenoantigens, which potentially represent new barriers for pig-to-human xenotransplantation. © 2009 Informa UK Ltd All rights reserved.