Identifying Epstein-Barr virus peptide sequences associated with differential IgG antibody response.
Identifying Epstein-Barr virus peptide sequences associated with differential IgG antibody response.
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DOI：
10.1016/j.ijid.2021.10.054
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Hildesheim A
中科院分区：
文献类型：
--
作者：
Coghill AE;Fang J;Liu Z;Chen CJ;Jarrett RF;Hjalgrim H;Proietti C;Yu KJ;Hsu WL;Lou PJ;Wang CP;Zhao Y;Doolan DL;Hildesheim A
EB病毒（EBV）感染有助于一部分血清阳性个体的癌症，但关于无癌成人EBV导向的体液免疫的变化仍有很多需要了解的。我们利用蛋白质微阵列来探测来自175名台湾人和141名北方欧洲成年人的血清，以获得对来自45种EBV蛋白的115种不同肽序列的IgG抗体应答，所述肽序列代表蛋白质片段或蛋白质变体。我们假设这种基于抗体的方法可以鉴定代表与B细胞免疫相关的免疫显性区域的EBV肽序列。对45种具有多个蛋白质片段或变体的EBV蛋白质的分析在阵列上鉴定了8种似乎在免疫原性中起作用的EBV肽序列。这包括（1）具有与IgG反应性相关的片段/区域的三种蛋白质（BALF 5、LMP 1、LMP 2A）和（2）具有与IgG反应性相关的序列变体/氨基酸变化的五种蛋白质（BLF 4、EBNA 3A、EBNA 3B、EBNA-LP、LF 1）。在316名无癌症的成年人中对115种EBV肽序列的IgG抗体反应的检查代表了鉴定在人类产生B细胞免疫中发挥作用的特定EBV蛋白序列的重要一步。我们利用全病毒组蛋白阵列来更好地理解（1）给定EB病毒（EBV）蛋白的不同区段和/或（2）所选EBV蛋白序列的不同变体（即，蛋白质片段中的氨基酸变化）在健康成人中引起不同的IgG抗体反应性。我们认为，这种方法将有助于确定EBV蛋白区域含有免疫显性表位，引发抗体介导的B细胞免疫。使用这种方法，我们在两个独立的人群中鉴定了8种具有至少一个与差异IgG抗体应答相关的序列的EBV蛋白，包括具有差异反应性片段的3种蛋白（BALF 5，LMP 1，LMP 2A）和具有改变IgG抗体应答的特定氨基酸变化的5种蛋白（BLF 4，EBNA 3A，EBNA 3B，EBNA-LP，LF 1）。我们的研究是迄今为止最大的EBV肽特异性IgG抗体应答的血清学调查，包括两个地理上不同的人群增加了研究结果的相关性。更全面地了解EBV指导的血清学库是设计基于EBV的诊断或治疗工具的重要一步。
Epstein-Barr virus (EBV) infection contributes to cancers in a fraction of seropositive individuals, but much remains to be learned about variation in EBV-directed humoral immunity in cancer-free adults. We leveraged a protein microarray to probe serum from 175 Taiwanese and 141 Northern European adults for IgG antibody responses to 115 different peptide sequences, representing protein segments or protein variants, from 45 EBV proteins. We posited that this antibody-based approach could identify EBV peptide sequences representing immunodominant regions relevant for B-cell immunity. Analyses of 45 EBV proteins with multiple protein segments or variants printed on the array identified eight EBV peptide sequences that appear to play a role in immunogenicity. This included (1) three proteins with segments/regions associated with IgG reactivity (BALF5, LMP1, LMP2A) and (2) five proteins with sequence variants/amino acid changes associated with IgG reactivity (BLF4, EBNA3A, EBNA3B, EBNA-LP, LF1). This examination of IgG antibody responses against 115 EBV peptide sequences in 316 cancer-free adults represents an important step toward identifying specific EBV protein sequences that play a role in generating B-cell immunity in humans. We utilized a virome-wide protein array to better understand whether (1) different segments of a given Epstein-Barr virus (EBV) protein and/or (2) different variants of select EBV protein sequences (i.e., amino acid changes in a protein segment) elicited differential IgG antibody reactivity in health adults. We posited that this approach would help identify EBV protein regionss containing immunodominant epitopes for eliciting antibody mediated B-cell immunity. Using this approach, we identified eight EBV proteins with at least one sequence associated with differential IgG antibody response, including three proteins with segments that were differentially reactive (BALF5, LMP1, LMP2A), and five proteins with specific amino acid changes that altered IgG antibody response (BLF4, EBNA3A, EBNA3B, EBNA-LP, LF1) in two independent populations. Our study is the largest serological survey of EBV peptide-specific IgG antibody responses to date, and the inclusion of two geographically distinct populations increases the relevance of study findings. A more complete understanding of the EBV-directed serological repertoire is an important step for the design of EBV-based diagnostic or therapeutic tools.
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影响因子：
3.8
作者：
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