Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy

Mark Slifka, Joseph N. Blattman, David J D Sourdive, Fei Liu, Donald L. Huffman, Tom Wolfe, Anna Hughes, Michael B A Oldstone, Rafi Ahmed, Matthias G. Von Herrath

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    Negative selection is designed to purge the immune system of high-avidity, self-reactive T cells and thereby protect the host from overt autoimmunity. In this in vivo viral infection model, we show that there is a previously unappreciated dichotomy involved in negative selection in which high-avidity CD8+ T cells specific for a dominant epitope are eliminated, whereas T cells specific for a subdominant epitope on the same protein preferentially escape deletion. Although this resulted in significant skewing of immunodominance and a substantial depletion of the most promiscuous T cells, thymic and/or peripheral deletion of high-avidity CD8+ T cells was not accompanied by any major change in the TCR Vβ gene family usage of an absolute deletion of a single preferred complementarity-determining region 3 length polymorphism. This suggests that negative selection allows high-avidity CD8+ T cells specific for subdominant or cryptic epitopes to persist while effectively deleting high-avidity T cells specific for dominant epitopes. By allowing the escape of subdominant T cells, this process still preserves a relatively broad peripheral TCR repertoire that can actively participate in antiviral and/or autoreactive immune responses.

    Original languageEnglish (US)
    Pages (from-to)1231-1239
    Number of pages9
    JournalJournal of Immunology
    Volume170
    Issue number3
    StatePublished - Feb 1 2003

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    Antiviral Agents
    T-Lymphocytes
    Epitopes
    Complementarity Determining Regions
    Virus Diseases
    Autoimmunity
    Immune System
    Genes
    Proteins

    ASJC Scopus subject areas

    • Immunology

    Cite this

    Slifka, M., Blattman, J. N., Sourdive, D. J. D., Liu, F., Huffman, D. L., Wolfe, T., ... Von Herrath, M. G. (2003). Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy. Journal of Immunology, 170(3), 1231-1239.

    Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy. / Slifka, Mark; Blattman, Joseph N.; Sourdive, David J D; Liu, Fei; Huffman, Donald L.; Wolfe, Tom; Hughes, Anna; Oldstone, Michael B A; Ahmed, Rafi; Von Herrath, Matthias G.

    In: Journal of Immunology, Vol. 170, No. 3, 01.02.2003, p. 1231-1239.

    Research output: Contribution to journalArticle

    Slifka, M, Blattman, JN, Sourdive, DJD, Liu, F, Huffman, DL, Wolfe, T, Hughes, A, Oldstone, MBA, Ahmed, R & Von Herrath, MG 2003, 'Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy', Journal of Immunology, vol. 170, no. 3, pp. 1231-1239.
    Slifka, Mark ; Blattman, Joseph N. ; Sourdive, David J D ; Liu, Fei ; Huffman, Donald L. ; Wolfe, Tom ; Hughes, Anna ; Oldstone, Michael B A ; Ahmed, Rafi ; Von Herrath, Matthias G. / Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy. In: Journal of Immunology. 2003 ; Vol. 170, No. 3. pp. 1231-1239.
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