Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response
Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response
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DOI：
10.1007/s00262-008-0456-y
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发表时间：
2008-08-01
影响因子：
5.8
通讯作者：
Marincola, Francesco M.
中科院分区：
文献类型：
--
作者：
Kanduc, Darja;Tessitore, Luciana;Marincola, Francesco M.
我们最近将HCV多蛋白与人类蛋白质组进行了比较，以测试病毒特有的氨基酸序列是否可以代表人类针对HCV的体液免疫反应的免疫显性表位决定因素。我们发现了相对有限数量的与人类宿主没有或低相似性的HCV片段，这些片段代表了独有的HCV基序。本研究合成了低/零相似序列对应的肽，并在hcv感染血清中进行了检测。不同模式下，低/零相似序列对应的合成HCV肽具有免疫反应性。特别是，HCV E1 (315-323) HRMAWDMMM、HCV E2/NS1 (547-555) NWFGCTWMN和HCV NS5 (2638-2646) YDTRCFDST序列在研究中的HCV感染队列中具有免疫优势。这三种肽对应的序列与人类蛋白质组具有低相似性，在各种HCV毒株中高度保守，并且可能对蛋白水解攻击具有稀少的易感性。这些数据可能有助于确定在调节人类抗丙型肝炎病毒免疫反应过程中共同存在的多种因素，最终为设计有效的抗丙型肝炎病毒疫苗提供信息。
We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera. With different patterns, the synthetic HCV peptides corresponding to low/zero similarity sequences were found to be immunoreactive. In particular, the HCV E1 (315-323) HRMAWDMMM, HCV E2/NS1 (547-555) NWFGCTWMN, and HCV NS5 (2638-2646) YDTRCFDST sequences were immunodominant in the HCV-infected cohort under study. These three peptides correspond to sequences that are endowed with low-similarity to the human proteome, are highly conserved among various HCV strains, and have, potentially, a scarce susceptibility to proteolytic attacks. These data may be of help in defining the multiple factors which concur in the modulation of the human immune response against HCV, eventually providing information for the design of effective anti-HCV vaccines.