Identification of CD8+ T cell epitopes in the West Nile virus polyprotein by reverse-immunology using NetCTL

PLoS One. 2010 Sep 14;5(9):e12697. doi: 10.1371/journal.pone.0012697.

Abstract

Background: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • CD8 Antigens / immunology
  • Cohort Studies
  • Computational Biology
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / analysis
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polyproteins / analysis
  • Polyproteins / genetics
  • Polyproteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • West Nile Fever / immunology
  • West Nile Fever / virology*
  • West Nile virus / chemistry
  • West Nile virus / genetics
  • West Nile virus / immunology*

Substances

  • CD8 Antigens
  • Epitopes, T-Lymphocyte
  • Polyproteins