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Modulation of αGal Epitope Expression on Porcine Cells

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 32))

Abstract

Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors (Auchincloss, 1988; Auchincloss, 1990; Auchincloss and Sachs, 1998; Sachs, 1994). The major barrier to successful clinical xenotransplantation is the lack of an effective way of eliminating antibody and complement, which mediate hyperacute rejection involving natural human antibodies to Galα(l,3)Gal (αGal). Numerous studies have shown that the major, antigen to which all humans have naturally occurring antibodies, and therefore of importance when pig tissue is transplanted to humans, is the αGal carbohydrate epitope (Good et al., 1992; Sandrin et al., 1993; Cooper et al., 1994; Sandrin and McKenzie, 1994; McKenzie et al., 1994b; Sandrin et al., 1994b). The phenomenon of hyperacute graft rejection and the importance of αGal in the pig-to-primate xenograft hyperacute rejection has been reviewed elsewhere (Cooper et al; 1994; Sandrin and McKenzie; 1994; Sandrin et al., 1994b). Here we examine the importance of the αGal epitope in xenograft rejection; describe the α1,3galac-tosyltransferase enzyme (αGT) responsible for generating αGal, and describe transgenic strategies designed to eliminate or reduce expression of αGal, such that the epitope is no longer recognised by natural human antibodies or indeed by human NK cells, which have been recently reported to recognise αGal (Artrip et al., 1998; Inverardi et al., 1997).

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© 1999 Springer Science+Business Media New York

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Sandrin, M.S., McKenzie, I.F.C. (1999). Modulation of αGal Epitope Expression on Porcine Cells. In: Galili, U., Avila, J.L. (eds) α-Gal and Anti-Gal. Subcellular Biochemistry, vol 32. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4771-6_13

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  • DOI: https://doi.org/10.1007/978-1-4615-4771-6_13

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