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Artigo em Inglês | MEDLINE | ID: mdl-27933274

RESUMO

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.


Assuntos
Epitopos de Linfócito T/imunologia , Antígenos H-2/isolamento & purificação , Antígenos H-2/farmacologia , Vírus Hantaan/imunologia , Febre Hemorrágica com Síndrome Renal/prevenção & controle , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Animais , Antígenos Virais/análise , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Linhagem Celular , Citocinas/análise , Testes Imunológicos de Citotoxicidade , Modelos Animais de Doenças , ELISPOT/métodos , Feminino , Glicoproteínas/efeitos dos fármacos , Glicoproteínas/imunologia , Vírus Hantaan/genética , Vírus Hantaan/patogenicidade , Febre Hemorrágica com Síndrome Renal/virologia , Imunização , Interferon gama/análise , Camundongos , Camundongos Endogâmicos C57BL , RNA Viral/isolamento & purificação , Baço/imunologia , Baço/patologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas
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