Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
PLoS One. 2010 Sep 14;5(9):e12697. doi: 10.1371/journal.pone.0012697.
West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.
METHODOLOGY/PRINCIPAL FINDINGS: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World.
CONCLUSIONS/SIGNIFICANCE: The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine.
西尼罗河病毒（WNV）对公共卫生构成了日益严重的威胁，深入了解针对 WNV 的免疫反应对于预防性和治疗性策略的开发至关重要。
方法/主要发现：在反向免疫学方法中，我们使用生物信息学方法来预测 WNV 特异性 CD8(+) T 细胞表位，并选择了一组最大限度地覆盖 20 个完全测序的 WNV 株的肽。然后，我们在一组 WNV 感染患者中测试了这些推测的表位的细胞反应性。我们确定了 26 个新的 CD8(+) T 细胞表位，我们提出这些表位受 11 种不同的 HLA Ⅰ类等位基因限制。为了最佳覆盖人群，我们建议这些新的 WNV 表位中的 11 个足以覆盖世界不同地区的 48%至 93%的种族群体。
结论/意义：鉴定出的 26 个 CD8(+) T 细胞表位有助于我们了解针对 WNV 感染的免疫反应，并大大扩展了已知的 WNV CD8(+) T 细胞表位列表。一个包含这些和其他表位的多面体可能可作为 WNV 疫苗的基础。
