Department of Veterinary Medicine: Medicine and Epidemiology, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA.
Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Sci Rep. 2017 May 26;7(1):2446. doi: 10.1038/s41598-017-02719-8.
Despite bovine pericardium (BP) being the primary biomaterial used in heart valve bioprostheses, recipient graft-specific immune responses remain a significant cause of graft failure. Consequently, tissue antigenicity remains the principal barrier for expanding use of such biomaterials in clinical practice. We hypothesize that our understanding of BP antigenicity can be improved by application of a combined affinity chromatography shotgun immunoproteomic approach to identify antigens that have previously been overlooked. Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) analysis of affinity chromatography purified antigens resulted in identification of 133 antigens. Most importantly, antigens were identified from all subcellular locations, including 18 integral membrane protein antigens. Critically, isoforms of several protein families were found to be antigenic suggesting the possibility that shared epitope domains may exist. Furthermore, proteins associated with immune, coagulation, and inflammatory pathways were over-represented, suggesting that these biological processes play a key role in antigenicity. This study brings to light important determinants of antigenicity in a clinically relevant xenogeneic biomaterial (i.e. BP) and further validates a rapid, high-throughput method for immunoproteomic antigen identification.
尽管牛心包（BP）是心脏瓣膜生物假体中使用的主要生物材料，但受者移植物特异性免疫反应仍然是移植物失败的重要原因。因此，组织抗原性仍然是限制此类生物材料在临床实践中广泛应用的主要障碍。我们假设，通过应用组合亲和层析 shotgun 免疫蛋白质组学方法，可以提高我们对 BP 抗原性的理解，从而识别以前被忽视的抗原。亲和层析纯化抗原的液相色谱串联质谱（LC-MS/MS）分析鉴定出 133 种抗原。最重要的是，从所有亚细胞位置鉴定出抗原，包括 18 种完整膜蛋白抗原。至关重要的是，发现几种蛋白家族的同工型具有抗原性，这表明可能存在共享表位结构域。此外，与免疫、凝血和炎症途径相关的蛋白质过度表达，表明这些生物学过程在抗原性中起着关键作用。这项研究揭示了临床相关异种生物材料（即 BP）中抗原性的重要决定因素，并进一步验证了一种快速、高通量的免疫蛋白质组学抗原鉴定方法。
