Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses

• 来源期刊: 中国病毒学
• 年，卷（期）: 2017,（4）
• 页码范围: 280-289
• 页数: 10页
• 语种: 英文
• DOI: 10.1007/s12250-017-3984-9

摘要

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 peptidespecific 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 ceils 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.