Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Bari, Italy,
Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Tel-Aviv, University School of Medicine, Ramat Gan, Israel.
Pathobiology. 2019;86(5-6):285-295. doi: 10.1159/000502889. Epub 2019 Oct 8.
To define the cross-reactivity potential and the consequent autoimmunity intrinsic to viral versus human peptide sharing.
Using human papillomavirus (HPV) infection/active immunization as a research model, the experimentally validated HPV L1 epitopes catalogued at the Immune Epitope DataBase were analyzed for peptide sharing with the human proteome.
The final data show that the totality of the immunoreactive HPV L1 epi-topes is mostly composed by peptides present in human proteins.
Immunologically, the high extent of peptide sharing between the HPV L1 epitopes and human proteins invites to revise the concept of the negative selection of self-reactive lymphocytes. Pathologically, the data highlight a cross-reactive potential for a spectrum of autoimmune diseases that includes ovarian failure, systemic lupus erythematosus (SLE), breast cancer and sudden death, among others. Therapeutically, analyzing already validated immunoreactive epitopes filters out the peptide sharing possibly exempt of self-reactivity, defines the effective potential for pathologic autoimmunity, and allows singling out peptide epitopes for safe immunotherapeutic protocols.
定义病毒与人类肽共享所固有 的交叉反应潜能和随之而来的自身免疫。
以人乳头瘤病毒(HPV)感染/主动免疫为研究模型,分析免疫表位数据库中经实验验证的 HPV L1 表位与人类蛋白质组之间的肽共享。
最终数据表明,大多数 HPV L1 免疫原性表位是由存在于人类蛋白质中的肽组成。
从免疫学角度来看,HPV L1 表位与人类蛋白质之间的肽共享程度很高,这使得人们有必要重新审视对自身反应性淋巴细胞的负选择概念。从病理学角度来看,这些数据强调了一系列自身免疫性疾病的交叉反应潜能,包括卵巢衰竭、系统性红斑狼疮(SLE)、乳腺癌和猝死等。从治疗学角度来看,分析已经验证的免疫原性表位可以筛选出可能无自身反应性的肽共享,确定病理性自身免疫的有效潜能,并可以挑选出安全免疫治疗方案的肽表位。