Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses

Andreansky, Samita S., Stambas, John, Thomas, Paul G., Xie, Weidong, Webby, Richard J. and Doherty, Peter C. 2005, Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses, Journal of Virology, vol. 79, no. 7, pp. 4329-4339.

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Title Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses
Author(s) Andreansky, Samita S.
Stambas, John
Thomas, Paul G.
Xie, Weidong
Webby, Richard J.
Doherty, Peter C.
Journal name Journal of Virology
Volume number 79
Issue number 7
Start page 4329
End page 4339
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2005
ISSN 0022-538X
Summary The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent DbNP366 and DbPA224 epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ KbPB1703+ , CD8+ KbNS2114+, and CD8+ DbPB1-F262+ T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the -NP-PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8+-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the -NP-PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8+ KbPB1703+ , CD8+ KbNS2114+, and CD8+ DbPB1-F262+ sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the -NP-PA deletion viruses. These findings have implications for both natural infections and vaccines.
Language eng
Field of Research 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies)
Socio Economic Objective 920108 Immune System and Allergy
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ┬ęCopyright 2005, American Society for Microbiology. All Rights Reserved.
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Document type: Journal Article
Collection: School of Medicine
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