Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3
Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3
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DOI：
10.1046/j.1365-2249.2000.01189.x
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发表时间：
2000-04-01
影响因子：
4.6
通讯作者：
Sugimoto, K
中科院分区：
文献类型：
--
作者：
Muro, Y;Azuma, N;Sugimoto, K
抗着丝粒自身抗体（ACA）常见于局限性硬皮病和其他系统性自身免疫性疾病患者的血清中。CENP-A是抗ACA和组蛋白h3样蛋白的主要抗原之一。为了分析CENP-A的自身抗原表位，我们在大肠杆菌中表达了一系列人CENP-A的截短肽，并对91份ACA（+）血清进行了免疫印迹分析。80份（88%）含有ACA的血清与非H3同源的52个氨基酸的n端反应，而没有一份与H3序列相似的c端反应。此外，本研究还利用酶联免疫吸附法合成了3-17（肽A）和25-38（肽B）氨基酸序列对应的两条肽段。肽A和B分别对78个（86%）和79个（87%）ACA有反应。乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）的核心抗原与肽A和/或肽B具有相似的序列，但3种含ACA的HBV血清和5种含ACA的HCV血清对这两种肽均无反应。CENP-A的着丝粒定位依赖于非自身抗原的h3样c端结构域，而抗原n端结构域可能起着未知的功能作用，可能是诱导ACA的重要区域。
Anti-centromere autoantibodies (ACA) are commonly found in the serum of patients with a limited type of scleroderma and other systemic autoimmune diseases. CENP-A is one of the major antigens against ACA and a histone H3-like protein. To analyse the autoantigenic epitopes of CENP-A, a series of truncated peptides of human CENP-A were expressed in Escherichia coli and immunoblotting analysis was performed with 91 ACA(+) sera. Eighty sera (88%) with the ACA reacted to the 52-amino acids N-terminal region which is not homologous to H3, while no sera reacted to the C-terminus which has a sequence similarity with H3. Moreover, ELISA was also employed in this study using two synthetic peptides corresponding to the amino acid sequences 3-17 (peptide A) and 25-38 (peptide B). Peptides A and B were reactive to 78 (86%) and 79 (87%) of ACA, respectively. Core antigens of hepatitis B virus (HBV) and hepatitis C virus (HCV) have similar sequences to peptide A and/or peptide B, but three sera containing HBV without ACA and five sera containing HCV without ACA were found to be reactive to neither peptide. Centromere localization of CENP-A is dependent on the H3-like C-terminal domain which is not autoantigenic, while the antigenic N-terminal domain, which might play unidentified functional roles, should be an important region for the induction of ACA.