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

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.

The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif

“…A more thorough evaluation for CfERV peptides in the future seems warranted. In humans, CTL have been demonstrated against ERV-derived peptides, supporting their presentation by HLA class I molecules (Mullins and Linnebacher, 2012; Schiavetti et al, 2002; Tu et al, 2017).…”

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma

“…Although peptides were used in many recent studies with concentrations ranging from 10–100 μg/ml, such as 20 μg/ml ( 51 ), 25 μg/ml ( 28 ), and 50 μg/ml ( 52 ), it is not always the case that the higher peptide concentration incubated DCs induced the higher activity of T cells. As early as 1964, Mitchison’s immunological study found that high immune doses often failed to induce ideal immune protection effect, which was called “high zone tolerance” ( 50 ).…”

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

“…Abundant interferon-γ-secreting T cells were also detected after stimulation of these peptides for several weeks. These data demonstrate that Syncytin-1 peptides (such as W, Q, and T peptides) can induce HLA-A2.1-restricted CD8 + CTL and could be a potential target for astrocytoma immunotherapy ( 98 ). On the other hand, the cytotoxic T lymphocytes induced by Syncytin-1 could be a potential mechanism for inflammatory abnormalities in the CNS.…”