title: Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.
abstract: Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral peptides in a lotion to human skin ("Peplotion") may be useful and affordable for populations of developing countries.
authors.affiliation: Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003715:Dengue / Q000517:prevention & control; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000517:prevention & control; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins