Fig. 1: Measuring the impact of different T cell co-signalling receptors on ligand sensitivity and discrimination. | Nature Biomedical Engineering

Fig. 1: Measuring the impact of different T cell co-signalling receptors on ligand sensitivity and discrimination.

From: Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors

Fig. 1

a, Experimental workflow to produce gene knockout primary human c259 TCR-T cells. b, Schematic of analysis method to determine the impact of gene knockout on ligand discrimination: changes in ligand potency between WT and KO TCR-T cells are plotted for different ligand affinities. Ligand potency (P15) is the ligand concentration required to activate 15% of maximum response. c, U87 cells were titrated with each of the 7 NY-ESO-1 peptides to stimulate WT or KO c259 TCR-T cells. Killing of the target U87 cells was measured after 20 h. Dashed line indicates potency (P15). Data in c are representative of at least N = 3 independent experiments with different blood donors. d, Fold change in P15 between KO and WT T cells from c plotted over the TCR–pMHC affinity (KD). Dashed line indicates fold change of 1. Data in d are shown as mean ± s.d. Significance of non-zero slope was assessed using a two-tailed F-test. NS, not significant; ***P < 0.001, ****P < 0.0001.

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