{"title":"HERV 衍生的 Syncytin-1 和 Syncytin-2 是抗磷脂综合征中线性和不连续表位的来源：一项关键的计算研究","authors":"Lorenzo Di Palma, Rossella Talotta","doi":"10.24976/Discov.Med.202436189.195","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>To date, no studies have investigated the potential reactivation of human endogenous retroviruses (HERVs) in the pathogenesis of antiphospholipid syndrome (APS). HERV-derived syncytin-1 and syncytin-2 are localized in the plasma membrane of cells and physiologically expressed during pregnancy. The current study aimed to determine whether the epitopes of syncytins can trigger an immune response leading to APS in genetically predisposed individuals.</p><p><strong>Methods: </strong>The TepiTool, ABCpred, and DiscoTope servers were utilized to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of syncytin-1, syncytin-2, and β2-glycoprotein I (β2GPI), which served as a reference antigen for APS. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) class II alleles associated with APS according to the literature. Epitope predictions for the different proteins were statistically compared using GraphPad Prism.</p><p><strong>Results: </strong>For syncytin-1, we identified a total of 721 T-cell epitopes, 51 linear B-cell epitopes, and up to 40 conformational epitopes. For syncytin-2, we predicted 705 T-cell epitopes and 28 linear B-cell epitopes, but a lower number of conformational epitopes, which also exhibited lower B-cell receptor (BCR)-binding scores. The predicted T-cell and B-cell conformational epitopes of both syncytin-1 and syncytin-2 demonstrated significantly higher binding affinity to selected HLA alleles and BCR compared with β2GPI. Furthermore, syncytin-1 exhibited significantly higher immunogenicity than syncytin-2.</p><p><strong>Conclusions: </strong>Both syncytin-1 and syncytin-2 are computationally endowed with potential epitopes that may activate either T cells or B cells in individuals genetically predisposed to APS. While these findings may illuminate the possible role of HERVs in the development of APS, they warrant validation in further laboratory studies.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 189","pages":"2111-2131"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HERV-Derived Syncytin-1 and Syncytin-2 as Sources of Linear and Discontinuous Epitopes in Antiphospholipid Syndrome: A Pivotal Computational Study.\",\"authors\":\"Lorenzo Di Palma, Rossella Talotta\",\"doi\":\"10.24976/Discov.Med.202436189.195\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>To date, no studies have investigated the potential reactivation of human endogenous retroviruses (HERVs) in the pathogenesis of antiphospholipid syndrome (APS). HERV-derived syncytin-1 and syncytin-2 are localized in the plasma membrane of cells and physiologically expressed during pregnancy. The current study aimed to determine whether the epitopes of syncytins can trigger an immune response leading to APS in genetically predisposed individuals.</p><p><strong>Methods: </strong>The TepiTool, ABCpred, and DiscoTope servers were utilized to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of syncytin-1, syncytin-2, and β2-glycoprotein I (β2GPI), which served as a reference antigen for APS. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) class II alleles associated with APS according to the literature. Epitope predictions for the different proteins were statistically compared using GraphPad Prism.</p><p><strong>Results: </strong>For syncytin-1, we identified a total of 721 T-cell epitopes, 51 linear B-cell epitopes, and up to 40 conformational epitopes. For syncytin-2, we predicted 705 T-cell epitopes and 28 linear B-cell epitopes, but a lower number of conformational epitopes, which also exhibited lower B-cell receptor (BCR)-binding scores. The predicted T-cell and B-cell conformational epitopes of both syncytin-1 and syncytin-2 demonstrated significantly higher binding affinity to selected HLA alleles and BCR compared with β2GPI. Furthermore, syncytin-1 exhibited significantly higher immunogenicity than syncytin-2.</p><p><strong>Conclusions: </strong>Both syncytin-1 and syncytin-2 are computationally endowed with potential epitopes that may activate either T cells or B cells in individuals genetically predisposed to APS. While these findings may illuminate the possible role of HERVs in the development of APS, they warrant validation in further laboratory studies.</p>\",\"PeriodicalId\":93980,\"journal\":{\"name\":\"Discovery medicine\",\"volume\":\"36 189\",\"pages\":\"2111-2131\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Discovery medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.24976/Discov.Med.202436189.195\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Discovery medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24976/Discov.Med.202436189.195","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景：迄今为止，尚无研究调查人类内源性逆转录病毒（HERVs）在抗磷脂综合征（APS）发病机制中的潜在再激活作用。HERV衍生的syncytin-1和syncytin-2定位于细胞质膜，在妊娠期有生理表达。目前的研究旨在确定 syncytins 的表位是否会引发免疫反应，从而导致遗传易感人群出现 APS：方法：通过输入 syncytin-1、syncytin-2 和作为 APS 参考抗原的β2-糖蛋白 I（β2GPI）的 FASTA 序列和三维结构，利用 TepiTool、ABCpred 和 DiscoTope 服务器预测 T 细胞和 B 细胞表位。根据文献，T细胞表位是根据它们与一组与APS相关的人类白细胞抗原（HLA）II类等位基因的结合情况选择的。使用 GraphPad Prism 对不同蛋白质的表位预测进行了统计比较：对于 syncytin-1，我们共鉴定出 721 个 T 细胞表位、51 个线性 B 细胞表位和多达 40 个构象表位。对于 syncytin-2，我们预测了 705 个 T 细胞表位和 28 个线性 B 细胞表位，但构象表位的数量较少，这些表位的 B 细胞受体（BCR）结合得分也较低。与β2GPI相比，syncytin-1和syncytin-2预测的T细胞和B细胞构象表位与选定的HLA等位基因和BCR的结合亲和力明显更高。此外，syncytin-1 的免疫原性明显高于 syncytin-2：结论：syncytin-1和syncytin-2在计算上都具有潜在的表位，可激活APS遗传易感者的T细胞或B细胞。这些发现可能揭示了 HERVs 在 APS 发病过程中可能扮演的角色，但还需要进一步的实验室研究加以验证。
HERV-Derived Syncytin-1 and Syncytin-2 as Sources of Linear and Discontinuous Epitopes in Antiphospholipid Syndrome: A Pivotal Computational Study.
Background: To date, no studies have investigated the potential reactivation of human endogenous retroviruses (HERVs) in the pathogenesis of antiphospholipid syndrome (APS). HERV-derived syncytin-1 and syncytin-2 are localized in the plasma membrane of cells and physiologically expressed during pregnancy. The current study aimed to determine whether the epitopes of syncytins can trigger an immune response leading to APS in genetically predisposed individuals.
Methods: The TepiTool, ABCpred, and DiscoTope servers were utilized to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of syncytin-1, syncytin-2, and β2-glycoprotein I (β2GPI), which served as a reference antigen for APS. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) class II alleles associated with APS according to the literature. Epitope predictions for the different proteins were statistically compared using GraphPad Prism.
Results: For syncytin-1, we identified a total of 721 T-cell epitopes, 51 linear B-cell epitopes, and up to 40 conformational epitopes. For syncytin-2, we predicted 705 T-cell epitopes and 28 linear B-cell epitopes, but a lower number of conformational epitopes, which also exhibited lower B-cell receptor (BCR)-binding scores. The predicted T-cell and B-cell conformational epitopes of both syncytin-1 and syncytin-2 demonstrated significantly higher binding affinity to selected HLA alleles and BCR compared with β2GPI. Furthermore, syncytin-1 exhibited significantly higher immunogenicity than syncytin-2.
Conclusions: Both syncytin-1 and syncytin-2 are computationally endowed with potential epitopes that may activate either T cells or B cells in individuals genetically predisposed to APS. While these findings may illuminate the possible role of HERVs in the development of APS, they warrant validation in further laboratory studies.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
