Protection and compensation in the influenza virus-specific CD8+ T cell response

Richard J. Webby, Samita Andreansky, John Stambast, Jerold E. Rehg, Robert G. Webster, Peter C. Doherty, Stephen J. Turner

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Influenza virus-specific CD8+ T cells generally recognize peptides derived from conserved, internal proteins that are not subject to antibody-mediated selection pressure. Prior exposure to any one influenza A virus (H1N1) can prime for a secondary CD8+ T cell response to a serologically different influenza A virus (H3N2). The protection afforded by this recall of established CD8+ T cell memory, although limited, is not negligible. Key characteristics of primary and secondary influenza-specific host responses are probed here with recombinant viruses expressing modified nucleoprotein (NP) and acid polymerase (PA) genes. Point mutations were introduced into the epitopes derived from the NP and PA such that they no longer bound the presenting H2Db MHC class I glycoprotein, and reassortant H1N1 and H3N2 viruses were made by reverse genetics. Conventional (C57BL/6J, H2b, and Ig+/+) and Ig-/- (μMT) mice were more susceptible to challenge with the single NP [HKx31 influenza A virus (HK)-NP] and PA (HK-PA) mutants, but unlike the Ig-/- mice, Ig+/+ mice were surprisingly resistant to the HK-NP/-PA double mutant. This virus was found to promote an enhanced IgG response resulting, perhaps, from the delayed elimination of antigen-presenting cells. Antigen persistence also could explain the increase in size of the minor KbPB1703 CD8+ T cell population in mice infected with the mutant viruses. The extent of such compensation was always partial, giving the impression that any virus-specific CD8+ T cell response operates within constrained limits. It seems that the relationship between protective humoral and cellular immunity is neither simple nor readily predicted.

Original languageEnglish
Pages (from-to)7235-7240
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number12
DOIs
StatePublished - Jun 10 2003
Externally publishedYes

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Orthomyxoviridae
Nucleoproteins
T-Lymphocytes
Viruses
Influenza A virus
Reassortant Viruses
H3N2 Subtype Influenza A Virus
Reverse Genetics
H1N1 Subtype Influenza A Virus
Antigen-Presenting Cells
Humoral Immunity
Point Mutation
Cellular Immunity
Human Influenza
Epitopes
Glycoproteins
Immunoglobulin G
Antigens
Pressure
Peptides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Protection and compensation in the influenza virus-specific CD8+ T cell response. / Webby, Richard J.; Andreansky, Samita; Stambast, John; Rehg, Jerold E.; Webster, Robert G.; Doherty, Peter C.; Turner, Stephen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 12, 10.06.2003, p. 7235-7240.

Research output: Contribution to journalArticle

Webby, Richard J. ; Andreansky, Samita ; Stambast, John ; Rehg, Jerold E. ; Webster, Robert G. ; Doherty, Peter C. ; Turner, Stephen J. / Protection and compensation in the influenza virus-specific CD8+ T cell response. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 12. pp. 7235-7240.
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