Details:

Alternative Title:
PLoS One
Personal Author:
Zhong, Weimin ; Liu, Feng ; Dong, Libo ; Lu, Xiuhua ; Hancock, Kathy ; ... More +
Zhong, Weimin ; Liu, Feng ; Dong, Libo ; Lu, Xiuhua ; Hancock, Kathy ; Reinherz, Ellis L. ; Katz, Jacqueline M. ; Sambhara, Suryaprakash Less -
Description:
Background

Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive 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.


Subject:
[+]
Amino Acid Sequence
Animals
Antibodies, Viral
CD8-Positive T-Lymphocytes
Cross-Priming
Cross Protection
Epitopes
Female
Genetic Variation
Humans
Immunity
Immunologic Memory
Immunology
Influenza, Human
Influenza A Virus
Lymphocyte Subsets
Mice
Molecular Sequence Data
Mucous Membrane
Nucleoproteins
Orthomyxoviridae Infections
Receptors, Antigen, T-Cell
Research Article
T-Lymphocytes, Cytotoxic
Viral Proteins

Source:
PLoS One. 5(5).
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:fe6881eabe45d4f94334f23e88d8db309917ed6f32462e92b2b1d392afa48a4a
File Type:

Supporting Files

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