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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

  • Research Article
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Virologica Sinica

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 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.

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Acknowledgments

This work was supported by grants from the National Natural Sciences Foundation of China (no. 31470264, no. 81271820, no. 30870789 and no. 30300117), the Key Program of the Natural Science Foundation of Hubei Province of China (no. 2014CFA078), the Stanley Foundation from the Stanley Medical Research Institute (SMRI), USA (no. 06R-1366), for Dr. F Zhu, and the Scientific Innovation Team Project of Hubei Province of China (no. 2015CFA009).

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Authors and Affiliations

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

    Xiaoning Tu, Ran Xiao, Xiuling Wang & Fan Zhu

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

    Shan Li

  3. Zhongnan Hospital of Wuhan University, Wuhan, 430060, China

    Lijuan Zhao

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

    Fan Zhu

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  1. Xiaoning Tu
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  2. Shan Li
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  3. Lijuan Zhao
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  4. Ran Xiao
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  5. Xiuling Wang
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  6. Fan Zhu
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Contributions

FZ designed the experiments. XNT, SL and RX carried out the experiments. LJZ provided the blood samples. XLW analyzed the date. XNT prepared the figures and/or tables and drafted the manuscript. FZ finalized the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fan Zhu.

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The authors declare that they have no conflict of interest.

The study was approved by the Ethics Committee of Wuhan University School of Medicine.

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Tu, X., Li, S., Zhao, L. et al. Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses. Virol. Sin. 32, 280–289 (2017). https://doi.org/10.1007/s12250-017-3984-9

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  • DOI: https://doi.org/10.1007/s12250-017-3984-9

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