West Nile Virus Infection: A Model for Human Epitope Immunodominance

Cytotoxic lymphocytes (CTL) have been shown to play an important role in the clearance of West Nile Virus (WNV), however no human CTL epitopes have been identified. Using a comparative mass spectrometric approach we identified six HLA‐A*0201 restricted viral‐derived peptides from five different viral proteins (Env, NS2b, NS3, NS4b, and NS5) that are presented during infection. All WNV peptide epitopes were of high affinity for HLA‐A*0201 and the epitope sequences were highly conserved among reported viral isolates. When these epitopes were tested with PBMC from WNV infected patients a hierarchy of reactive epitopes emerged. In the majority of the infected patients tested (65%), a peptide from the envelope glycoprotein of WNV was the immunodominant epitope. Furthermore 82.5% of the patients reacted to more than one epitope such that a clear hierarchy emerges among WNV CTL epitopes. This pattern is reiterated in animal models. In summary, we report the detection of endogenous WNV class I HLA peptide epitopes, we characterize these epitopes recognition by CTL, and we identify a pattern of immunodominance that is consistent among humans and animal models.