Abstract：
Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs. While therapeutics exist that can help mitigate the detrimental effects of antibodies, they act broadly potentially dampening beneficial immunity. Identifying additional xenoantigens may enable more targeted approaches, such as gene editing, to overcome these challenges by further eliminating antibody targets on donor tissue. Because we have found that classical class I swine leukocyte antigens are targets of human antibodies, we now examine whether related pig proteins may also be targeted by human antibodies. We show here that non-classical class I swine leukocyte proteins (SLA-6, -7, -8) can be expressed at the surface of mammalian cells and act as antibody targets.
摘要：
众所周知，预先形成的抗猪抗体对供体组织的攻击会导致异种移植中的移植物失败。对猪供体进行基因工程以消除这些预先形成的抗体的靶标，再加上免疫抑制药物的进步，现在可以在临床前猪到非人灵长类动物模型中实现延长的存活。尽管有这些改进,抗体在移植的一生中仍然存在风险，和许多患者继续预先形成的供体特异性抗体，甚至高度工程化的猪。虽然存在可以帮助减轻抗体有害影响的疗法，他们的行为广泛可能削弱有益的免疫力。识别额外的异种抗原可以实现更有针对性的方法，比如基因编辑，通过进一步消除供体组织上的抗体靶标来克服这些挑战。因为我们发现经典的I类猪白细胞抗原是人类抗体的靶标，我们现在研究相关的猪蛋白是否也可能被人类抗体靶向。我们在这里表明，非经典I类猪白细胞蛋白（SLA-6，-7，-8）可以在哺乳动物细胞表面表达并充当抗体靶标。
