Chemical inhibitors suggest that TCR downregulation is dependent on multiple tyrosine kinases. Human CD4+PBLs were stimulated with anti‐CD3/CD28 in the presence of protein tyrosine kinase inhibitors PP2, dasatinib, or imatinib. (A–C) Representative histograms of surface TCRβ (A), total TCRζ (B) expression, and surface CD69 (C) expression. (D–F) Aggregate data normalized to the unstimulated control for n = 3 individual donors examined in a single experiment, with the median and 95% CI depicted. (G) Lentiviral and retroviral microRNA vectors and lentiviral CRISPR/Cas9 vectors for knockdown of TCRζ (CD247) expression. CI, confidence interval; MFI, mean fluorescence intensity; PBL, peripheral blood lymphocytes; TCR, T‐cell receptor. Statistics were calculated by one‐way analysis of variance followed by Tukey's test for multiple comparisons, *p < .05; **p < .005; ***p < .001; ****p < .0001