Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses
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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.
KeywordsHuman endogenous retrovirus W (HERV-W) env peptide HLA CTL
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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).
- Dervillez X, Qureshi H, Chentoufi AA, Khan AA, Kritzer E, Yu DC, Diaz OR, Gottimukkala C, Kalantari M, Villacres MC et al., 2013. Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes. J Immunol, 191: 5124–5138.CrossRefPubMedPubMedCentralGoogle Scholar
- Drexhage RC, Hoogenboezem TA, Cohen D, Versnel MA, Nolen WA, van Beveren NJ, Drexhage HA. 2011. An activated set point of T-cell and monocyte inflammatory networks in recentonset schizophrenia patients involves both pro- and anti-inflammatory forces. Int J Neuropsychopharmacol, 14: 746–755.CrossRefPubMedGoogle Scholar
- Kessler JH, Mommaas B, Mutis T, Huijbers I, Vissers D, Benckhuijsen WE, Schreuder GM, Offringa R, Goulmy E, Melief CJ, van der Burg SH, Drijfhout JW. 2003. Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides. Hum Immunol, 64: 245–255.CrossRefPubMedGoogle Scholar
- Perron H, Dougier-Reynaud HL, Lomparski C, Popa I, Firouzi R, Bertrand JB, Marusic S, Portoukalian J, Jouvin-Marche E, Villiers CL, Touraine JL, Marche PN. 2013. Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice. PLoS One, 8: e80128.CrossRefPubMedPubMedCentralGoogle Scholar
- Perron H, Jouvin-Marche E, Michel M, Ounanian-Paraz A, Camelo S, Dumon A, et al. 2001. Multiple sclerosis retrovirus particles and recombinant envelope trigger an abnormal immune response in vitro, by inducing polyclonal Vbeta16 T-lymphocyte activation. Virology, 287: 321–332.CrossRefPubMedGoogle Scholar
- Seyed N, Zahedifard F, Safaiyan S, Gholami E, Doustdari F, Azadmanesh K, Mirzaei M, Saeedi Eslami N, Khadem Sadegh A, Eslami Far A, Sharifi I, Rafati S. 2011. In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response. PLoS Negl Trop Dis, 5: e1295.CrossRefPubMedPubMedCentralGoogle Scholar