Protective capacity and epitope specificity of CD8+ T cells responding to lethal West Nile virus infection

James D. Brien, Jennifer L. Uhrlaub, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the Flaviviridae genus, which causes lethal encephalitis in a subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and mortality, but the basis of this effect is unclear, and the molecular and cellular parameters of the host-WNV infection are just beginning to be elucidated. Indeed, numerous mechanisms were implicated in protection in vivo against WNV (IFN-I and IFN-γ, antibody, C', CD8 and CD4 T cells), but the individual importance of each one of these remains unclear. Here, we show that transfer of highly enriched naïve CD8+ T cells protects the majority of alymphoid mice against lethal WNV infection. To substantiate and expand this finding, we defined the peptide specificity of the CD8 response in H-2b mice and used a panel of identified peptides to map one dominant (NS4b 2248-2256) and several subdominant epitopes. The hierarchy of these epitopes was stably maintained in the memory responses. Most importantly, CTL lines directed against these peptides conferred protection against lethal WNV infection in direct proportion to the epitope immunodominance. These results provide a springboard for future characterization of T cell responses against WNV and demonstrate, for the first time, that CD8 T cells can single-handedly protect from this disease.

Original languageEnglish (US)
Pages (from-to)1855-1863
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor Specificity
West Nile virus
Virus Diseases
Epitopes
T-Lymphocytes
Peptides
Flaviviridae
RNA Viruses
Encephalitis
Birds
Mammals
Morbidity
Mortality
Antibodies

Keywords

  • CD8 T cells
  • Infectious diseases
  • Virology
  • West Nile virus

ASJC Scopus subject areas

  • Immunology

Cite this

Protective capacity and epitope specificity of CD8+ T cells responding to lethal West Nile virus infection. / Brien, James D.; Uhrlaub, Jennifer L.; Nikolich-Zugich, Janko.

In: European Journal of Immunology, Vol. 37, No. 7, 07.2007, p. 1855-1863.

Research output: Contribution to journalArticle

@article{5f58859f080040caac10b4304777c0a5,
title = "Protective capacity and epitope specificity of CD8+ T cells responding to lethal West Nile virus infection",
abstract = "West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the Flaviviridae genus, which causes lethal encephalitis in a subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and mortality, but the basis of this effect is unclear, and the molecular and cellular parameters of the host-WNV infection are just beginning to be elucidated. Indeed, numerous mechanisms were implicated in protection in vivo against WNV (IFN-I and IFN-γ, antibody, C', CD8 and CD4 T cells), but the individual importance of each one of these remains unclear. Here, we show that transfer of highly enriched na{\"i}ve CD8+ T cells protects the majority of alymphoid mice against lethal WNV infection. To substantiate and expand this finding, we defined the peptide specificity of the CD8 response in H-2b mice and used a panel of identified peptides to map one dominant (NS4b 2248-2256) and several subdominant epitopes. The hierarchy of these epitopes was stably maintained in the memory responses. Most importantly, CTL lines directed against these peptides conferred protection against lethal WNV infection in direct proportion to the epitope immunodominance. These results provide a springboard for future characterization of T cell responses against WNV and demonstrate, for the first time, that CD8 T cells can single-handedly protect from this disease.",
keywords = "CD8 T cells, Infectious diseases, Virology, West Nile virus",
author = "Brien, {James D.} and Uhrlaub, {Jennifer L.} and Janko Nikolich-Zugich",
year = "2007",
month = "7",
doi = "10.1002/eji.200737196",
language = "English (US)",
volume = "37",
pages = "1855--1863",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "7",

}

TY - JOUR

T1 - Protective capacity and epitope specificity of CD8+ T cells responding to lethal West Nile virus infection

AU - Brien, James D.

AU - Uhrlaub, Jennifer L.

AU - Nikolich-Zugich, Janko

PY - 2007/7

Y1 - 2007/7

N2 - West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the Flaviviridae genus, which causes lethal encephalitis in a subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and mortality, but the basis of this effect is unclear, and the molecular and cellular parameters of the host-WNV infection are just beginning to be elucidated. Indeed, numerous mechanisms were implicated in protection in vivo against WNV (IFN-I and IFN-γ, antibody, C', CD8 and CD4 T cells), but the individual importance of each one of these remains unclear. Here, we show that transfer of highly enriched naïve CD8+ T cells protects the majority of alymphoid mice against lethal WNV infection. To substantiate and expand this finding, we defined the peptide specificity of the CD8 response in H-2b mice and used a panel of identified peptides to map one dominant (NS4b 2248-2256) and several subdominant epitopes. The hierarchy of these epitopes was stably maintained in the memory responses. Most importantly, CTL lines directed against these peptides conferred protection against lethal WNV infection in direct proportion to the epitope immunodominance. These results provide a springboard for future characterization of T cell responses against WNV and demonstrate, for the first time, that CD8 T cells can single-handedly protect from this disease.

AB - West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the Flaviviridae genus, which causes lethal encephalitis in a subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and mortality, but the basis of this effect is unclear, and the molecular and cellular parameters of the host-WNV infection are just beginning to be elucidated. Indeed, numerous mechanisms were implicated in protection in vivo against WNV (IFN-I and IFN-γ, antibody, C', CD8 and CD4 T cells), but the individual importance of each one of these remains unclear. Here, we show that transfer of highly enriched naïve CD8+ T cells protects the majority of alymphoid mice against lethal WNV infection. To substantiate and expand this finding, we defined the peptide specificity of the CD8 response in H-2b mice and used a panel of identified peptides to map one dominant (NS4b 2248-2256) and several subdominant epitopes. The hierarchy of these epitopes was stably maintained in the memory responses. Most importantly, CTL lines directed against these peptides conferred protection against lethal WNV infection in direct proportion to the epitope immunodominance. These results provide a springboard for future characterization of T cell responses against WNV and demonstrate, for the first time, that CD8 T cells can single-handedly protect from this disease.

KW - CD8 T cells

KW - Infectious diseases

KW - Virology

KW - West Nile virus

UR - http://www.scopus.com/inward/record.url?scp=34447557656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447557656&partnerID=8YFLogxK

U2 - 10.1002/eji.200737196

DO - 10.1002/eji.200737196

M3 - Article

C2 - 17559175

AN - SCOPUS:34447557656

VL - 37

SP - 1855

EP - 1863

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 7

ER -