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

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    Author
    Crowe, SR; Turner, SJ; Miller, SC; Roberts, AD; Rappolo, RA; Doherty, PC; Ely, KH; Woodland, DL
    Date
    2003-08-04
    Source Title
    JOURNAL OF EXPERIMENTAL MEDICINE
    Publisher
    ROCKEFELLER UNIV PRESS
    University of Melbourne Author/s
    Turner, Stephen; Doherty, Peter
    Affiliation
    Microbiology And Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Crowe, S. R., Turner, S. J., Miller, S. C., Roberts, A. D., Rappolo, R. A., Doherty, P. C., Ely, K. H. & Woodland, D. L. (2003). Differential antigen presentation regulates the changing patterns of CD8(+) T cell immunodominance in primary and secondary influenza virus infections. JOURNAL OF EXPERIMENTAL MEDICINE, 198 (3), pp.399-410. https://doi.org/10.1084/jem.20022151.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/26616
    DOI
    10.1084/jem.20022151
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194086
    Description

    C1 - Journal Articles Refereed

    Abstract
    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.
    Keywords
    Cellular Immunology; Immune System and Allergy

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