title: Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus.
abstract: The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-Kb-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-Kb. Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-Kb-restricted CTL epitope with involvement in the host immune response to HTNV infection.
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Ma
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Cheng
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Qi-Kang
authors.initials: QK
authors.lastname: Ying
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Ma
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Zhi-Kai
authors.initials: ZK
authors.lastname: Xu
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Xing-An
authors.initials: XA
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000187:drug effects / Q000276:immunology; D006183:H-2 Antigens / Q000302:isolation & purification* / Q000494:pharmacology*; D018063:Hantaan virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006480:Hemorrhagic Fever with Renal Syndrome / Q000517:prevention & control* / Q000821:virology; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D012367:RNA, Viral; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
keywords: HTNV; IFN-γ; epitope; glycoprotein; infection