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

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 6024-6032, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.00009-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Hypervariable Immunodominant NP_418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity

Adrianus C. M. Boon, Gerrie de Mutsert, Ron A. M. Fouchier, Albert D. M. E. Osterhaus, and Guus F. Rimmelzwaan^*

Department of Virology, Postgraduate School Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands

Received 3 January 2006/ Accepted 22 March 2006

Recently it was shown that influenza A viruses can accumulate mutations in epitopes associated with escape from recognition by human virus-specific cytotoxic T lymphocytes (CTL). It is unclear what drives diversification of CTL epitopes and why certain epitopes are variable and others remain conserved. It has been shown that simian immunodeficiency virus-specific CTL that recognize their epitope with high functional avidity eliminate virus-infected cells efficiently and drive diversification of CTL epitopes. T-cell functional avidity is defined by the density of major histocompatibility complex class I peptide complexes required to activate specific CTL. We hypothesized that functional avidity of CTL contributes to epitope diversification and escape from CTL also for influenza viruses. To test this hypothesis, the functional avidity of polyclonal CTL populations specific for nine individual epitopes was determined. To this end, peripheral blood mononuclear cells from HLA-A- and -B-genotyped individuals were stimulated in vitro with influenza virus-infected cells to allow expansion of virus-specific CTL, which were used to determine the functional avidity of CTL specific for nine individual epitopes in enzyme-linked immunospot assays. We found that the functional avidity for the respective epitopes varied widely. Furthermore, the functional avidity of CTL specific for the hypervariable NP_418-426 epitope was significantly higher than that of CTL recognizing other epitopes (P < 0.01). It was speculated that the high functional avidity of NP_418-426-specific CTL was responsible for the diversification of this influenza A virus CTL epitope.

---

* Corresponding author. Mailing address: Erasmus MC, Department of Virology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31 10 4088243. Fax: 31 10 4089485. E-mail: g.rimmelzwaan{at}erasmusmc.nl.

Present address: Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.

---

Journal of Virology, June 2006, p. 6024-6032, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.00009-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Wahl, A., Schafer, F., Bardet, W., Buchli, R., Air, G. M., Hildebrand, W. H. (2009). HLA class I molecules consistently present internal influenza epitopes. Proc. Natl. Acad. Sci. USA 106: 540-545 [Abstract] [Full Text]  
• Ng, A. K.-L., Zhang, H., Tan, K., Li, Z., Liu, J.-h., Chan, P. K.-S., Li, S.-M., Chan, W.-Y., Au, S. W.-N., Joachimiak, A., Walz, T., Wang, J.-H., Shaw, P.-C. (2008). Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. FASEB J. 22: 3638-3647 [Abstract] [Full Text]