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Artículo en Inglés | MEDLINE | ID: mdl-27933274

RESUMEN

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.


Asunto(s)
Epítopos de Linfocito T/inmunología , Antígenos H-2/aislamiento & purificación , Antígenos H-2/farmacología , Virus Hantaan/inmunología , Fiebre Hemorrágica con Síndrome Renal/prevención & control , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Animales , Antígenos Virales/análisis , Antígenos Virales/inmunología , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Línea Celular , Citocinas/análisis , Pruebas Inmunológicas de Citotoxicidad , Modelos Animales de Enfermedad , Ensayo de Immunospot Ligado a Enzimas/métodos , Femenino , Glicoproteínas/efectos de los fármacos , Glicoproteínas/inmunología , Virus Hantaan/genética , Virus Hantaan/patogenicidad , Fiebre Hemorrágica con Síndrome Renal/virología , Inmunización , Interferón gamma/análisis , Ratones , Ratones Endogámicos C57BL , ARN Viral/aislamiento & purificación , Bazo/inmunología , Bazo/patología , Vacunas de Subunidad/inmunología , Vacunas Sintéticas
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