Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58.

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58.
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表观组学:来自致癌人乳头瘤病毒 58 型的 E6、E7 和 L1 蛋白的 IgG 表观组解码

DOI:
10.1038/srep34686
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发表时间:
2016-10-06
期刊:
影响因子:
4.6
通讯作者:
Xie Y
Xie Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu WX;Wang J;Tang HP;He YP;Zhu QX;Gupta SK;Gu SH;Huang Q;Ji CN;Liu LF;Li GL;Xu CJ;Xie Y

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为了设计合理的多表位疫苗和诊断抗原,描述完整的免疫球蛋白表位势在必行。在这里,我们描述了来自高危致癌的人乳头瘤病毒58型(HPV58)的三种蛋白的免疫球蛋白表位解码结果。为了揭示它们的完整表位,采用多肽生物合成法,利用兔抗E6、E7和L1重组蛋白的血清,将30个精确的线性B细胞表位(BCE)定位在E6、E7和L1蛋白上。基于BCE最小基序的序列比对,每个定位的BCE的特异性和保守性主要在已知的HR-HPV中描述,包括发现3个广泛的抗体交叉反应的L1 BCE,每个都覆盖几乎所有的HR-HPV。免疫印迹显示,L1表位内的18个BCEs中有13个能被小鼠抗HPV58病毒样颗粒血清识别,提示这些BCEs是抗体可及的BCEs。此外,E6的一个高度保守的表位(YGD/XTL)仅存在于已知的常见HR-HPV中,可作为判断HR-HPV的第一个肽参考标志。综上所述,本研究提供了关于HR-HPV58线性BCEs的系统和详尽的信息,这将有助于开发用于检测病毒抗体的新型多表位诊断试剂/芯片和基于L1保守BCEs的‘通用’预防性HPV多肽疫苗。
To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs.
DOI: 10.1016/s1470-2045(10)70230-8
发表时间: 2010-11-01
期刊: LANCET ONCOLOGY
影响因子: 51.1
作者:
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影响因子: 4.1
作者:
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