The Journal of Experimental Medicine
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Published online 28 July 2003 doi:10.1084/jem.20022151
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© Rockefeller University Press, 0022-1007/2003/8/399 $5.00
The Journal of Experimental Medicine, Volume 198, Number 3, 399-410

Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

Sherry R. Crowe1, Stephen J. Turner2, Shannon C. Miller1, Alan D. Roberts1, Rachel A. Rappolo1, Peter C. Doherty2, Kenneth H. Ely1 and David L. Woodland1

1 Trudeau Institute, Saranac Lake, NY 12983
2 Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia

Address correspondence to David L. Woodland, Trudeau Institute, P.O. Box 59, Saranac Lake, NY 12983. Phone: 518-891-3080; Fax: 518-891-5126; email: dwoodland{at}trudeauinstitute.org

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.

Key Words: antigen-presenting cells • antigen presentation • CD8-positive T lymphocytes • influenza • immunologic memory


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