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

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

    Research output: Contribution to journalArticlepeer-review

    93 Citations (Scopus)


    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
    Issue number5
    Publication statusPublished - May 23 2013

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases


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