Genome-wide CRISPR screen correctly identifies known regulators of proximal TCR signaling. Genome-wide CRISPR screen correctly identifies known regulators.

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Genome-wide CRISPR screen correctly identifies known regulators of proximal TCR signaling. Genome-wide CRISPR screen correctly identifies known regulators of proximal TCR signaling. (A) CRISPR targeting Zap70 impaired T cell activation. After lentiviral transduction of sgRNA in Cas9-expressing Jurkat cells, intracellular Zap70 expression (Upper) and surface CD69 expression after TCR stimulation were assessed using flow cytometry (Lower). (B) Workflow of the CRISPR-based screen. (C) The abundance of sgRNAs against Cbl, Zap70, and NTC in both CD69high and CD69low samples. (D) Cumulative density functions of gene rank for the 43 known positive regulators of the TCR pathway (red) and all other genes (blue). (E) Components of the TCR signaling pathway derived from ref. 10 and their ranks in our screen (blue scale). Wanjing Shang et al. PNAS 2018;115:17:E4051-E4060 ©2018 by National Academy of Sciences