West Nile Virus T-Cell Ligand Sequences Shared with Other Flaviviruses: a Multitude of Variant Sequences as Potential Altered Peptide Ligands

Phylogenetic relatedness and cocirculation of several major human pathogen flaviviruses are recognized as a possible cause of deleterious immune responses to mixed infection or immunization and call for a greater understanding of the inter-Flavivirus protein homologies. This study focused on the identification of human leukocyte antigen (HLA)-restrictedWest Nile virus (WNV) T-cell ligands and characterization of their distribution in reported sequence data ofWNV and other flaviviruses. H-2-deficient mice transgenic for either A2, A24, B7, DR2, DR3, or DR4 HLA alleles were immunized with overlapping peptides of the WNV proteome, and peptide-specific T-cell activation was measured by gamma interferon (IFN-) enzyme-linked immunosor-bent spot (ELISpot) assays. Approximately 30 % (137) of theWNV proteome peptides were identified as HLA-restricted T-cell ligands. The majority of these ligands were conserved in>88 % of analyzedWNV sequences. Notably, only 51 wereWNV spe-cific, and the remaining 86, chiefly of E, NS3, and NS5, shared an identity of nine or more consecutive amino acids with se