Abstract
Abstract We previously characterized an immunodomiant, HLA-A*0201 restricted, West Nile virus (WNV) peptide determinant. This dominant WNV peptide epitope, termed SVG9, lies within a highly conserved region of the envelope glycoprotein and demonstrates 100% homology among contemporary WNV strains. This region of the virus envelope is also highly conserved among other Flaviviruses such as Japanese encephalitis virus and Dengue virus (DV). Since immune cross reactivity has been reported within the Dengue virus serogroup, we hypothesized that T cells specific for this A*0201 restricted WNV stretch of envelope would cross-recognize different flaviviruses due to epitope conservation. As an initial test of this hypothesis we synthesized the corresponding envelope peptide for WNV (SVG9) and DV type 1 (SIG9). We utilized a competitive peptide binding assay to demonstrate that SVG9 and SIG9 have comparable and high A*0201 binding affinities. We then utilized PBMC from WNV and DV1 seropositive donors to assess T cell cross recognition of SVG9 and SIG9. T cells specific for the WNV SVG9 were cross-reactive for their DV1 Flaviviral counterpart SIG 9 and vice versa. These data demonstrate that cellular immunity is cross-reactive among different Flaviviruses. This observation has implications for vaccine development and for unraveling the immunopathology associated with infection.
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