Human leukemia antigen-A0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses
Human leukemia antigen-A0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses
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人内源性逆转录病毒 W 家族包膜 (HERV-W env) 的人白血病抗原 A0201 限制性表位诱导强烈的细胞毒性 T 淋巴细胞反应
DOI：
10.1007/s12250-017-3984-9
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发表时间：
2017
影响因子：
5.5
通讯作者：
通讯作者）
中科院分区：
文献类型：
--
作者：
Tu Xiaoning;Li Shan;Zhao Lijuan;Xiao Ran;Wang Xiuling;Zhu Fan（朱帆;通讯作者）
人内源性逆转录病毒W家族（HERV-W）包膜蛋白（env）与多种人类疾病有关，并能激活先天免疫，其中包括自身免疫性疾病。然而，还没有研究人类白血病抗原（HLA）-A*0201+限制是否参与神经精神疾病中HERV-W env引起的免疫应答的报道。在本研究中，HERV-W env衍生的HLA-A*0201表位被描述为具有用于过继免疫治疗的潜力。使用SYFEPITHI和BIMAS预测并合成了显示HLA-A*0201结合基序的五个肽。CCK-8法显示肽W、Q和T促进淋巴细胞增殖。用这些肽中的每一种刺激来自HLA-A*0201+供体的外周血单核细胞诱导肽特异性CD 8 +T细胞。在W、Q和T每周刺激几次后，也可检测到大量分泌IFN-γ的T细胞。除了HERV-W env负载的靶细胞的裂解之外，还观察到特异性凋亡。这些数据表明，人T细胞可以对HERV-W env肽（W、Q和T）敏感，并且此外，对表达HERV-W env的U251细胞具有高杀伤潜力。结论：HERV-W env抗原表位W Q和T肽具有抗原性和免疫原性，能引起较强的T细胞免疫应答。我们的数据加强了HERV-W env应该被认为是一种自身抗原，可以诱导神经精神疾病，如多发性硬化症和精神分裂症的自身免疫。这些数据可能为HERV-W env肽疫苗的研究提供实验基础，并为神经精神疾病的治疗提供新的见解。
Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201+restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLA-A*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A*0201+donors with each of these peptides induced peptide-specific CD8+T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.