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Journal of Virology, August 2008, p. 7768-7772, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00653-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Simple Mathematical Model Helps To Explain the Immunodominance of CD8 T Cells in Influenza A Virus Infections{triangledown}

Andreas Handel* and Rustom Antia

Department of Biology, Emory University, Atlanta, Georgia 30322

Received 24 March 2008/ Accepted 30 May 2008

Understanding immunodominance, the phenomenon of epitope-specific T cells expanding in an often distinctly hierarchical fashion, is important for the design of T-cell-based intervention strategies. Several recent studies have investigated immunodominance of H-2Db-restricted CD8+ T cells specific for the nucleoprotein NP366 and acid polymerase PA224 epitopes during influenza A virus infection of C57BL/6 mice. CD8+ T cells specific for these two epitopes are codominant during primary infection; NP366 dominates during secondary infection. While a number of explanations for this observation have been proposed, none of them can fully account for all the observed data. In this article, we use a simple mathematical model to explain the seemingly inconsistent data. We show that the dynamic interactions between CD8+ T cells and antigen presentation lead to a situation where CD8+ T cells are limiting during the initial response whereas antigen is limiting in the secondary response. This "numbers game" between antigen and CD8+ T cells can reproduce the observed immunodominance of the NP336- and PA224-specific CD8+ T cells, thereby explaining the reported experimental data.

* Corresponding author. Mailing address: Emory University, Department of Biology, 1510 Clifton Road NE, Atlanta, GA 30322. Phone: (404) 727-1765. Fax: (404) 727-2880. E-mail: ahandel{at}emory.edu

{triangledown} Published ahead of print on 11 June 2008.

Journal of Virology, August 2008, p. 7768-7772, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00653-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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