Extended Data Fig. 1: Quality control of the CRISPR screens.

a, Fluorescence activated cell sorting (FACS) gating for IL2RA, IL-2, and CTLA4 screens. Representative example from the IL2RA screen is shown. b, Abundance of sgRNAs targeting GFP in either the starting plasmid or in the GFP + sorted population (n = 3 donors, 1 plasmid pool). c, Differential enrichment between the high- and low-expression bins for sgRNAs targeting genes that are either expressed or not expressed in CD4 + T cells based on RNA-Seq. d, Abundance of sgRNAs targeting essential genes, fitness genes, non-essential genes, or non-targeting guides in the starting plasmid (n = 1) or in the GFP + sorted samples (n = 3 donors). e, Enrichment of sgRNAs between the GFP + sorted population and starting plasmid. Results from Donor 1 and Donor 2 are depicted. Significant hits were identified with MAGeCK and genes with an FDR-adjusted P < 0.05 across all donors are highlighted. f, Comparison of the number of shared significant hits between the different screens and whether those hits have the same direction of effect on their targets. Two-sided sign test P = 0.002, shared direction of effect = 82%, 95% confidence interval 61-95%. All boxplots show the median, first and third quartiles, and 1.5x the interquartile range.