Epitopes described in "HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D."

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Article Authors:Aziz Alami Chentoufi; Xiuli Zhang; Kasper Lamberth; Gargi Dasgupta; Ilham Bettahi; Alex Nguyen; Michelle Wu; Xiaoming Zhu; Amir Mohebbi; Søren Buus; Steven L Wechsler; Anthony B Nesburn; Lbachir Benmohamed
Article Title:HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
Reference Detail
Reference ID:1007943
Abstract:Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10 amino acids in length, exhibited high-affinity binding in vitro to purified human HLA-A*0201 molecules. Three of these four peptide epitopes, gD53-61, gD70-78, and gD278-286, significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes. In addition, CD8+ T cell lines generated by gD53-61, gD70-78, and gD278-286 peptides recognized infected target cells expressing native gD. Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.
Affiliations:Laboratory of Cellular and Molecular Immunology, Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697, USA.
Date:2008
Reference Type:Literature
PubMed ID:18097044
Journal:J Immunol
Journal Volume:180
Article Pages:426-37
Journal ISSN:0022-1767
Article Chemical List:Antigens, CD8;Epitopes, T-Lymphocyte;HLA-A Antigens;HLA-A*0201 antigen;Herpesvirus Vaccines;Peptides;Viral Envelope Proteins;glycoprotein D, Human herpesvirus 1;glycoprotein D-herpes simplex virus type 2;herpes simplex virus-1 glycoprotein D vaccine
Article MeSH List:Animals; Antigens, CD8(analysis ); Computational Biology; Cytotoxicity, Immunologic; Epitope Mapping; Epitopes, T-Lymphocyte(chemistry; immunology ); Female; HLA-A Antigens(chemistry; genetics; immunology ); Herpesvirus Vaccines(chemistry; immunology ); Humans; Male; Mice; Mice, Transgenic; Peptides(genetics; immunology ); T-Lymphocytes, Cytotoxic(immunology ); Viral Envelope Proteins(chemistry; immunology )
Curation Last Updated:2009-11-09 19:30:51