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

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

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

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

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

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

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

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

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

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

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