Human leukemia antigen-A0201-restricted epitopes of humanendogenous retrovirus W family envelope （HERV-W env） inducestrong cytotoxic T lymphocyte responses

摘要

Human endogenous retrovirus W family （HERV-W） envelope （env） has been reported to be relatedto 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 neuropsychiatricdiseases. In the present study, HERV-W env-derived epitopes presented by HLA-A＊0201 aredescribed 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-8assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheralblood mononuclear cells from HLA-A＊0201＊ donors with each of these peptides induced peptide-specific CD8＊ T cells. High numbers of IFN-y-secreting T cells were also detectable after severalweekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specificapoptosis was also observed. These data demonstrate that human T cells can be sensitized towardHERV-W env peptides （W, Q and T） and, moreover, pose a high killing potential toward HERV-Wenv-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenicepitopes, have both antigenicity and immunogenicity, and can cause strong T cell immuneresponses. Our data strengthen the view that HERV-W env should be considered as an autoantigenthat can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis andschizophrenia. These data might provide an experimental foundation for a HERV-W env peptidevaccine and new insight into the treatment of neuropsychiatric diseases.