This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andreansky, S. S.
Right arrow Articles by Doherty, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andreansky, S. S.
Right arrow Articles by Doherty, P. C.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4329-4339, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4329-4339.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Consequences of Immunodominant Epitope Deletion for Minor Influenza Virus-Specific CD8+-T-Cell Responses

Samita S. Andreansky,1,{dagger} John Stambas,1,2,{dagger} Paul G. Thomas,1 Weidong Xie,1 Richard J. Webby,3 and Peter C. Doherty1,2*

Departments of Immunology,1 Infectious Disease, St. Jude Children's Research Hospital, Memphis, Tennessee,3 Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia2

Received 4 June 2004/ Accepted 3 November 2004

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.

* Corresponding author. Mailing address: Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Phone: (901) 495-3480. Fax: (901) 495-3107. E-mail: peter.doherty{at}stjude.org.

{dagger} S.S.A. and J.S. contributed equally to these experiments.

Journal of Virology, April 2005, p. 4329-4339, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4329-4339.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fryer, H. R., Scherer, A., Oxenius, A., Phillips, R., McLean, A. R. (2009). No evidence for competition between cytotoxic T-lymphocyte responses in HIV-1 infection. Proc R Soc B 276: 4389-4397 [Abstract] [Full Text]  
  • Munitic, I., Decaluwe, H., Evaristo, C., Lemos, S., Wlodarczyk, M., Worth, A., Le Bon, A., Selin, L. K., Riviere, Y., Di Santo, J. P., Borrow, P., Rocha, B. (2009). Epitope Specificity and Relative Clonal Abundance Do Not Affect CD8 Differentiation Patterns during Lymphocytic Choriomeningitis Virus Infection. J. Virol. 83: 11795-11807 [Abstract] [Full Text]  
  • Sexton, A., De Rose, R., Reece, J. C., Alcantara, S., Loh, L., Moffat, J. M., Laurie, K., Hurt, A., Doherty, P. C., Turner, S. J., Kent, S. J., Stambas, J. (2009). Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques. J. Virol. 83: 7619-7628 [Abstract] [Full Text]  
  • Handel, A., Antia, R. (2008). A Simple Mathematical Model Helps To Explain the Immunodominance of CD8 T Cells in Influenza A Virus Infections. J. Virol. 82: 7768-7772 [Abstract] [Full Text]  
  • Kotturi, M. F., Scott, I., Wolfe, T., Peters, B., Sidney, J., Cheroutre, H., von Herrath, M. G., Buchmeier, M. J., Grey, H., Sette, A. (2008). Naive Precursor Frequencies and MHC Binding Rather Than the Degree of Epitope Diversity Shape CD8+ T Cell Immunodominance. J. Immunol. 181: 2124-2133 [Abstract] [Full Text]  
  • Neumann-Haefelin, C., Frick, D. N., Wang, J. J., Pybus, O. G., Salloum, S., Narula, G. S., Eckart, A., Biezynski, A., Eiermann, T., Klenerman, P., Viazov, S., Roggendorf, M., Thimme, R., Reiser, M., Timm, J. (2008). Analysis of the Evolutionary Forces in an Immunodominant CD8 Epitope in Hepatitis C Virus at a Population Level. J. Virol. 82: 3438-3451 [Abstract] [Full Text]  
  • Vallbracht, S., Jessen, B., Mrusek, S., Enders, A., Collins, P. L., Ehl, S., Krempl, C. D. (2007). Influence of a Single Viral Epitope on T Cell Response and Disease After Infection of Mice with Respiratory Syncytial Virus. J. Immunol. 179: 8264-8273 [Abstract] [Full Text]  
  • Assarsson, E., Sidney, J., Oseroff, C., Pasquetto, V., Bui, H.-H., Frahm, N., Brander, C., Peters, B., Grey, H., Sette, A. (2007). A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection. J. Immunol. 178: 7890-7901 [Abstract] [Full Text]  
  • Lee, S., Miller, S. A., Wright, D. W., Rock, M. T., Crowe, J. E. Jr. (2007). Tissue-Specific Regulation of CD8+ T-Lymphocyte Immunodominance in Respiratory Syncytial Virus Infection. J. Virol. 81: 2349-2358 [Abstract] [Full Text]  
  • Thomas, P. G., Brown, S. A., Keating, R., Yue, W., Morris, M. Y., So, J., Webby, R. J., Doherty, P. C. (2007). Hidden Epitopes Emerge in Secondary Influenza Virus-Specific CD8+ T Cell Reponses. J. Immunol. 178: 3091-3098 [Abstract] [Full Text]  
  • Jenkins, M. R., Webby, R., Doherty, P. C., Turner, S. J. (2006). Addition of a Prominent Epitope Affects Influenza A Virus-Specific CD8+ T Cell Immunodominance Hierarchies When Antigen Is Limiting.. J. Immunol. 177: 2917-2925 [Abstract] [Full Text]  
  • Thomas, P. G., Brown, S. A., Yue, W., So, J., Webby, R. J., Doherty, P. C. (2006). An unexpected antibody response to an engineered influenza virus modifies CD8+ T cell responses. Proc. Natl. Acad. Sci. USA 103: 2764-2769 [Abstract] [Full Text]  
  • La Gruta, N. L., Kedzierska, K., Pang, K., Webby, R., Davenport, M., Chen, W., Turner, S. J., Doherty, P. C. (2006). A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. Proc. Natl. Acad. Sci. USA 103: 994-999 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»