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Key Roles of Calcium Signaling in T Cell Activation: Mechanisms and Pathways

Explore the early rise in intracellular calcium levels upon TCR engagement and its critical role in T cell activation. Learn about the pharmacological and genetic evidence supporting this process, as well as the signaling pathways involved in calcium release and entry. Understand the requirements for calcium signal duration and amplitude, and the impact on TCR-responsive gene expression. Discover the cooperative nature of IP3-induced calcium release and the involvement of CRAC channels in TCR-triggered calcium entry.

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Key Roles of Calcium Signaling in T Cell Activation: Mechanisms and Pathways

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  1. Engagement of the TCR causes an early rise in [Ca2+]i Population response Tsien et al, 1982 Single-cell response (FACS)

  2. Single-cell responses (imaging) Negulescu et al, 1996

  3. The [Ca2+]i rise is necessary for T cell activation I. Pharmacological evidence Chung et al, 1994

  4. Le Diest et al, 1995 The [Ca2+]i rise is necessary for T cell activation II. Genetic evidence

  5. The [Ca2+]i rise (with PKC activation) is sufficient to induce TCR-responsive genes Diehn et al, 2002

  6. Duration and amplitude requirements for the Ca2+ signal Dolmetsch et al, 1998 Negulescu et al, 1994

  7. Generation of the Ca2+ signal by antigen recognition I. IP3-induced Ca2+ release Winslow et al, 2003 IP3 Imboden & Stobo, 1985

  8. IP3-induced Ca2+ release is highly cooperative Jurkat cells IP3 receptors in planar lipid bilayer Bezprozvanny et al, 1991

  9. TCR engagement triggers “capacitative” (store-operated) Ca2+ entry in lymphocytes Mason et al, 1991

  10. Premack et al, 1994 TCR engagement stimulates Ca2+ entry via the CRAC channel Zweifach and Lewis, 1993

  11. CRAC channels are the sole Ca2+ entry pathway triggered through the TCR mutagenize Jurkat NFAT/dipA Ca Ca X dipA survival Ionomycin + PdBU Fanger et al, 1995 (Also see Partiseti et al, 1994; Feske et al, 2001)

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