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Glycobiology, Vol 9, 865-873, Copyright © 1999 by Oxford University Press

ORIGINAL ARTICLES

Naturally occurring anti-alpha-galactosyl antibodies: relationship to xenoreactive anti-alpha-galactosyl antibodies

W Parker, SS Lin, PB Yu, A Sood, YC Nakamura, A Song, ML Everett and JL Platt
Department of Surgery, Departments of Surgery and Immunology, and Departments of Surgery, Immunology, and Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

Antibodies produced by an individual without a known history of sensitization to the relevant antigen are called "natural" antibodies. Some natural antibodies, called xenoreactive antibodies, react with the cells of foreign species. Most xenoreactive antibodies in humans and higher primates bind to a nonreducing terminal galactose expressed by pigs and other lower mammals. Although human natural antibodies which bind to one or more of a variety of terminal alpha-galactosylstructures have been identified previously, the antigen recognized by anti-alpha- galactosyl antibodies on the cells of foreign species is thought to be exclusively Galalpha1-3Gal. Thus, anti-alpha-galactosyl antibodies which do not react with Galalpha1-3Gal are thought to be nonxenoreactive. Here, we identify natural antibodies in human serum which bind to Galalpha1-6Hexosepyrranosides but not Galalpha1-3Gal, indicating that these antibodies are not xenoreactive. Various lowermammals were found to have natural anti-Galalpha1-2Galantibodies in their sera, suggesting that at least some anti-Galalpha1-2Gal antibodies might not be xenoreactive andindicating, surprisingly, that anti-alpha-galactosyl antibodies are much more phylogenetically disperse than previously known. Also surprising was the finding that some natural antibodies which bind to Galalpha1-3Gal in vitro do not bind to porcine xenografts. These studies show that naturally occurring anti-alpha-galactosyl antibodies in mammalian serum include antibodies with a greater variety of reactivities than previously thought, only some of which would bind to a porcine xenograft. Further, these studies show that the methods used todetect anti-alpha-galactosyl antibodies of relevance in xenotransplantation must be carefully evaluated to avoid detection of anti-alpha-galactosyl antibodies which would not bind to a porcine organ and which therefore are not involved in xenograft rejection.
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M. Duk, U. Westerlind, T. Norberg, G. Pazynina, N. N. Bovin, and E. Lisowska
Specificity of human anti-NOR antibodies, a distinct species of "natural" anti-{alpha}-galactosyl antibodies
Glycobiology, April 1, 2003; 13(4): 279 - 284.
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