Kanduc Darja, Tessitore Luciana, Lucchese Guglielmo, Kusalik Anthony, Farber Emanuel, Marincola Francesco M
Infectious Diseases and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Cancer Immunol Immunother. 2008 Aug;57(8):1215-23. doi: 10.1007/s00262-008-0456-y. Epub 2008 Feb 7.
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.
我们最近将丙型肝炎病毒（HCV）多聚蛋白与人类蛋白质组进行了比较，以测试该病毒特有的氨基酸序列是否可能代表人类针对HCV的体液免疫反应的免疫显性表位决定簇。我们鉴定出了相对数量有限的与人类宿主无/低相似性的HCV片段，这些片段代表了HCV独有的基序。在本研究中，合成了与低/零相似性序列对应的肽段，并用HCV感染患者的血清进行检测。结果发现，与低/零相似性序列对应的合成HCV肽段呈现出不同的反应模式，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序列在所研究的HCV感染队列中具有免疫显性。这三个肽段对应的序列与人类蛋白质组的相似性较低，在各种HCV毒株中高度保守，并且可能对蛋白水解攻击的敏感性较低。这些数据可能有助于确定影响人类针对HCV免疫反应调节的多种因素，最终为设计有效的抗HCV疫苗提供信息。
