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

Samita Andreansky, John Stambas, Paul G. Thomas, Weidong Xie, Richard J. Webby, Peter C. Doherty

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent D bNP366 and DbPA224epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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-CeIl 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+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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.

Original languageEnglish
Pages (from-to)4329-4339
Number of pages11
JournalJournal of Virology
Volume79
Issue number7
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

Immunodominant Epitopes
Orthomyxoviridae
T-lymphocytes
Influenza A virus
H3N2 Subtype Influenza A Virus
Viruses
T-Lymphocytes
viruses
primary contact
Enzyme-Linked Immunospot Assay
Reverse Genetics
H1N1 Subtype Influenza A Virus
Bronchoalveolar Lavage
Population
epitopes
Epitopes
spleen
cytokines
Vaccines
Spleen

ASJC Scopus subject areas

  • Immunology

Cite this

Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses. / Andreansky, Samita; Stambas, John; Thomas, Paul G.; Xie, Weidong; Webby, Richard J.; Doherty, Peter C.

In: Journal of Virology, Vol. 79, No. 7, 01.04.2005, p. 4329-4339.

Research output: Contribution to journalArticle

Andreansky, Samita ; Stambas, John ; Thomas, Paul G. ; Xie, Weidong ; Webby, Richard J. ; Doherty, Peter C. / Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses. In: Journal of Virology. 2005 ; Vol. 79, No. 7. pp. 4329-4339.
@article{f422e155749740e49948b047044afeb9,
title = "Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses",
abstract = "The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent D bNP366 and DbPA224epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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-CeIl 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+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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.",
author = "Samita Andreansky and John Stambas and Thomas, {Paul G.} and Weidong Xie and Webby, {Richard J.} and Doherty, {Peter C.}",
year = "2005",
month = "4",
day = "1",
doi = "10.1128/JVI.79.7.4329-4339.2005",
language = "English",
volume = "79",
pages = "4329--4339",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses

AU - Andreansky, Samita

AU - Stambas, John

AU - Thomas, Paul G.

AU - Xie, Weidong

AU - Webby, Richard J.

AU - Doherty, Peter C.

PY - 2005/4/1

Y1 - 2005/4/1

N2 - The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent D bNP366 and DbPA224epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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-CeIl 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+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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.

AB - The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent D bNP366 and DbPA224epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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-CeIl 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+ K bPB1703+, CD8+ KbNS2 114+, and CD8+ DbPB1-F2 62+ 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.

UR - http://www.scopus.com/inward/record.url?scp=15244345880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15244345880&partnerID=8YFLogxK

U2 - 10.1128/JVI.79.7.4329-4339.2005

DO - 10.1128/JVI.79.7.4329-4339.2005

M3 - Article

C2 - 15767433

AN - SCOPUS:15244345880

VL - 79

SP - 4329

EP - 4339

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -