McKenzie I F, Patton K, Smit J A, Mouhtouris E, Xing P, Myburgh J A, Sandrin M S
Molecular Immunogenetics Laboratory, Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Transplantation. 1999 Mar 27;67(6):864-70. doi: 10.1097/00007890-199903270-00013.
The Gal alpha(1,3)Gal epitope is of interest as, in pig-to-primate xenotransplantation, it is the major target of naturally occurring human IgM and IgG antibodies, leading to hyperacute rejection. Human and Old World monkeys make anti-Gal alpha(1,3)Gal antibodies as they lack a functional gene and do not express Gal alpha(1,3)Gal. Interestingly, the cultured fibroblasts of some other species, such as chickens, have been reported also not to express Gal alpha(1,3)Gal--if this is true for other tissues, and chickens do not express Gal alpha(1,3)Gal antigen, then they would have anti-Gal antibodies--which could have diagnostic and therapeutic value, particularly as chicken antibodies do not fix mammalian complement.
Standard serological methods were used to characterize the antibodies. Several baboons received pig kidney xenografts that had been perfused with hyperimmune chicken anti-Gal antibodies.
We now demonstrate that chickens do not express Gal alpha(1,3)Gal on their red cells, leukocytes, or tissues, and that their serum contains large amounts of anti-Gal alpha(1,3)Gal antibodies. In addition, chickens could be immunized to produce high-titer, high-avidity antibodies (9.5x10(9) M(-1))--an avidity considerably greater than that of the Gal alpha(1,3)Gal binding lectin IB4 (2.9x10(8) M(-1)) or Gal antibodies in human serum (2.2x10(5) M(-1)). Chicken antibodies, obtained from both normal and immunized chickens, could block the in vitro cytolysis of pig endothelial cells or lymphocytes by human or baboon antibodies. However, such antibodies tested in vivo in pig-to-baboon xenotransplantation failed to block hyperacute rejection and, indeed, may have accelerated this.
α-半乳糖（α1,3）表位备受关注，因为在猪到灵长类动物的异种移植中，它是天然存在的人类IgM和IgG抗体的主要靶点，会导致超急性排斥反应。人类和旧世界猴会产生抗α-半乳糖（α1,3）抗体，因为它们缺乏功能性基因且不表达α-半乳糖（α1,3）。有趣的是，据报道其他一些物种（如鸡）的培养成纤维细胞也不表达α-半乳糖（α1,3）——如果其他组织也是如此，且鸡不表达α-半乳糖（α1,3）抗原，那么它们会有抗α-半乳糖抗体——这可能具有诊断和治疗价值，特别是因为鸡抗体不固定哺乳动物补体。
使用标准血清学方法对抗体进行表征。几只狒狒接受了用超免疫鸡抗α-半乳糖抗体灌注的猪肾异种移植物。
我们现在证明鸡的红细胞、白细胞或组织上不表达α-半乳糖（α1,3），且它们的血清含有大量抗α-半乳糖（α1,3）抗体。此外，鸡可以被免疫以产生高滴度、高亲和力的抗体（9.5×10⁹ M⁻¹）——亲和力远高于α-半乳糖（α1,3）结合凝集素IB4（2.9×10⁸ M⁻¹）或人血清中的α-半乳糖抗体（2.2×10⁵ M⁻¹）。从正常鸡和免疫鸡获得的鸡抗体可以阻断人或狒狒抗体对猪内皮细胞或淋巴细胞的体外细胞溶解作用。然而，在猪到狒狒异种移植的体内实验中，这些抗体未能阻断超急性排斥反应，实际上，可能还加速了这种反应。
