Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis

Whitney E. Purtha, Nancy Myers, Vesselin Mitaksov, Elizabeth Sitati, Janet Connolly, Daved H. Fremont, Ted H. Hansen, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Infection with West Nile virus (WNV) causes fatal encephalitis in immunocompromised animals. Previous studies in mice have established that T cell protection is required for clearance of WNV infection from tissues and preventing viral persistence. The current study assessed whether specific WNV peptide epitopes could elicit a cytotoxic T lymphocyte (CTL) response capable of protecting against virus infection. Hidden Markov model analysis was used to identify WNV-encoded peptides that bound the MHC class I proteins Kb or Db Of the 35 peptides predicted to bind MHC class I molecules, one immunodominant CTL recognition peptide was identified in each of the envelope and non-structural protein 4B genes. Addition of these but not control peptides to CD8+ T cells from WNV-infected mice induced IFN- production. CTL clones that were generated ex vivo lysed peptide-pulsed or WNV-infected target cells in an antigen-specific manner. Finally, adoptive transfer of a mixture of envelope- and non-structural protein 4B-specific CTL to recipient mice protected against lethal WNV challenge. Based on this, we conclude that CTL responses against immundominant WNV epitopes confer protective immunity and thus should be targets for inclusion in new vaccines.

Original languageEnglish
Pages (from-to)1845-1854
Number of pages10
JournalEuropean Journal of Immunology
Volume37
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • Antigen presentation
  • Cytotoxic T cells
  • Peptide epitopes
  • Virus

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