Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry

Masatsugu Ohora, Noriko Komatsu, Mojgan Pishyareh, Stefan Feske, Shohei Hori, Masaru Taniguchi, Anjana Rao, Hiroshi Takayanagi

    Research output: Contribution to journalArticle

    68 Citations (Scopus)

    Abstract

    T cell receptor (TCR) signaling driven by interaction of the TCR with specific complexes of self-peptide and the major histocompatibility complex determines T cell fate in thymic development. However, the signaling pathway through which TCR signal strength regulates distinct T cell lineages remains unknown. Here we have used mice lacking the endoplasmic reticulum Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2 to show that STIM-induced store-operated Ca2+ entry is not essential for thymic development of conventional TCRαβ+ T cells but is specifically required for the development of agonist-selected T cells (regulatory T cells, invariant natural killer T cells, and TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes). The severe impairment of agonist-selected T cell development is mainly due to a defect in interleukin-2 (IL-2) or IL-15 signaling. Thus, STIM1 and STIM2-mediated store-operated Ca2+ influx, leading to efficient activation of NFAT (nuclear factor of activated T cells), is critical for the postselection maturation of agonist-selected T cells.

    Original languageEnglish
    Pages (from-to)881-895
    Number of pages15
    JournalImmunity
    Volume38
    Issue number5
    DOIs
    Publication statusPublished - May 23 2013

    Fingerprint

    T-Cell Antigen Receptor
    Calcium
    T-Lymphocytes
    NFATC Transcription Factors
    Interleukin-15
    Natural Killer T-Cells
    Cell Lineage
    Regulatory T-Lymphocytes
    Major Histocompatibility Complex
    Endoplasmic Reticulum
    Interleukin-2
    Lymphocytes
    Peptides

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

    Cite this

    Ohora, M., Komatsu, N., Pishyareh, M., Feske, S., Hori, S., Taniguchi, M., ... Takayanagi, H. (2013). Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry. Immunity, 38(5), 881-895. https://doi.org/10.1016/j.immuni.2013.02.008

    Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry. / Ohora, Masatsugu; Komatsu, Noriko; Pishyareh, Mojgan; Feske, Stefan; Hori, Shohei; Taniguchi, Masaru; Rao, Anjana; Takayanagi, Hiroshi.

    In: Immunity, Vol. 38, No. 5, 23.05.2013, p. 881-895.

    Research output: Contribution to journalArticle

    Ohora, M, Komatsu, N, Pishyareh, M, Feske, S, Hori, S, Taniguchi, M, Rao, A & Takayanagi, H 2013, 'Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry', Immunity, vol. 38, no. 5, pp. 881-895. https://doi.org/10.1016/j.immuni.2013.02.008
    Ohora, Masatsugu ; Komatsu, Noriko ; Pishyareh, Mojgan ; Feske, Stefan ; Hori, Shohei ; Taniguchi, Masaru ; Rao, Anjana ; Takayanagi, Hiroshi. / Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry. In: Immunity. 2013 ; Vol. 38, No. 5. pp. 881-895.
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