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Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections.
- Source :
-
PLoS ONE . 2010, Vol. 5 Issue 5, p1-10. 10p. 1 Chart, 5 Graphs. - Publication Year :
- 2010
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Abstract
- Background: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly crossreactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. Methodology/Principal Findings: We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP366/Db epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP366/Db variants was significantly lower than those triggered by the homologous NP366/Db ligand. It appears that strict specificity of a dominant public TCR to the original NP366/Db ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP366/Db variants. Conclusions/Significance: Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 52682171
- Full Text :
- https://doi.org/10.1371/journal.pone.0010583