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

TY - JOUR

T1 - Identification of CD8+ T cell epitopes in the West Nile virus polyprotein by reverse-immunology using NetCTL

AU - Larsen, Mette Voldby

AU - Lelic, Alina

AU - Parsons, Robin

AU - Nielsen, Morten

AU - Hoof, Ilka

AU - Lamberth, Kasper

AU - Loeb, Mark B

AU - Buus, Søren

AU - Bramson, Jonathan

AU - Lund, Ole

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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 WNVspecific 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.

AB - 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 WNVspecific 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.

KW - Adult

KW - Aged

KW - Amino Acid Sequence

KW - Antigens, CD8

KW - Cohort Studies

KW - Computational Biology

KW - Epitope Mapping

KW - Epitopes, T-Lymphocyte

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Polyproteins

KW - T-Lymphocytes, Cytotoxic

KW - West Nile Fever

KW - West Nile virus

U2 - 10.1371/journal.pone.0012697

DO - 10.1371/journal.pone.0012697

M3 - Journal article

C2 - 20856867

SN - 1932-6203

VL - 5

SP - e12697

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 9

ER -