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


RESULTS
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
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.
Larsen
Mette Voldby
MV
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. metteb@cbs.dtu.dk
Lelic
Alina
A
Parsons
Robin
R
Nielsen
Morten
M
Hoof
Ilka
I
Lamberth
Kasper
K
Loeb
Mark B
MB
Buus
Søren
S
Bramson
Jonathan
J
Lund
Ole
O
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D016827:CD8 Antigens / Q000276:immunology; D015331:Cohort Studies; D019295:Computational Biology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020815:Polyproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology / Q000821:virology*; D014902:West Nile virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D020815:Polyproteins