Differential antigen presentation regulates the changing patterns of CD8 + T cell immunodominance in primary and secondary influenza virus infections

Sherry R. Crowe, Stephen J. Turner, Shannon C. Miller, Alan D. Roberts, Rachel A. Rappolo, Peter C. Doherty, Kenneth H. Ely, David L. Woodland

Research output: Contribution to journalArticleResearchpeer-review

181 Citations (Scopus)

Abstract

The specificity of CD8 + T cell responses can vary dramatically between primary and secondary infections. For example, NP 366-374 /D b - and PA 224-233 /D b -specific CD8 + T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP 366-374 /D b -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 NP 366-374 /D b epitope, whereas only dendritic cells effectively present the PA 224-233 /D b epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP 366-374 /D b -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 PA 224-233 /D b , that are poorly expressed at the site of infection. In this regard, vaccination with the PA 224-233 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.

Original languageEnglish
Pages (from-to)399-410
Number of pages12
JournalJournal of Experimental Medicine
Volume198
Issue number3
DOIs
Publication statusPublished - 4 Aug 2003
Externally publishedYes

Keywords

  • Antigen presentation
  • Antigen-presenting cells
  • CD8-positive T lymphocytes
  • Immunologic memory
  • Influenza

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