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Volume 32 Issue 4
August 2017
    Citation: Xiaoning Tu, Shan Li, Lijuan Zhao, Ran Xiao, Xiuling Wang, Fan Zhu. Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses .VIROLOGICA SINICA, 2017, 32(4) : 280-289.  http://dx.doi.org/10.1007/s12250-017-3984-9
    shu

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

    Identification of HLA restricted epitopes of HERV-W env

    cstr: 32224.14.s12250-017-3984-9
    • 1.

      Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, China

    • 2.

      Department of Integrated Medicine, Dongfeng Hospital, Hubei University of Medicine, Hubei 442000, China

    • 3.

      Zhongnan Hospital of Wuhan University, Wuhan 430060, China

    • 4.

      Hubei Province Key Laboratory of Allergy and Immunology, Wuhan 430071, China

    • Corresponding author: Fan Zhu, fanzhu@whu.edu.cn, ORCID: 0000-0001-7031-2956
    • Received Date: 24 March 2017
      Accepted Date: 20 July 2017
      Published Date: 22 August 2017
      Available online: 01 August 2017
    • 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 HLAA*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 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.
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      Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses

        Corresponding author: Fan Zhu, fanzhu@whu.edu.cn
      • 1. Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, China
      • 2. Department of Integrated Medicine, Dongfeng Hospital, Hubei University of Medicine, Hubei 442000, China
      • 3. Zhongnan Hospital of Wuhan University, Wuhan 430060, China
      • 4. Hubei Province Key Laboratory of Allergy and Immunology, Wuhan 430071, China
      • Received Date: 24 March 2017
      • Accepted Date: 20 July 2017
      • Published Date: 22 August 2017

      Abstract: 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 HLAA*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 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.

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