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• W1993298907 endingPage "2016" @default.
• W1993298907 startingPage "2011" @default.
• W1993298907 abstract "For efficient development of an immune response, T lymphocytes require long-lasting calcium influx through calcium release-activated calcium (CRAC) channels and the formation of a stable immunological synapse (IS) with the antigen-presenting cell (APC). Recent RNAi screens have identified Stim and Orai in Drosophila cells, and their corresponding mammalian homologs STIM1 and Orai1 in T cells, as essential for CRAC channel activation. Here, we show that STIM1 and Orai1 are recruited to the immunological synapse between primary human T cells and autologous dendritic cells. Both STIM1 and Orai1 accumulated in the area of contact between either resting or super-antigen (SEB)-pretreated T cells and SEB-pulsed dendritic cells, where they were colocalized with T cell receptor (TCR) and costimulatory molecules. In addition, imaging of intracellular calcium signaling in T cells loaded with EGTA revealed significantly higher Ca 2+ concentration near the interface, indicating Ca 2+ influx localized at the T cell/dendritic cell contact area. Expression of a dominant-negative Orai1 mutant blocked T cell Ca 2+ signaling but did not interfere with the initial accumulation of STIM1, Orai1, and CD3 in the contact zone. In activated T cell blasts, mRNA expression for endogenous STIM1 and all three human homologs of Orai was up-regulated, accompanied by a marked increase in Ca 2+ influx through CRAC channels. These results imply a positive feedback loop in which an initial TCR signal favors up-regulation of STIM1 and Orai proteins that would augment Ca 2+ signaling during subsequent antigen encounter." @default.
• W1993298907 created "2016-06-24" @default.
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• W1993298907 date "2008-02-12" @default.
• W1993298907 modified "2023-10-03" @default.
• W1993298907 title "Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation" @default.
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• W1993298907 doi "https://doi.org/10.1073/pnas.0706122105" @default.
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