The FE11 γδTCR critically depends on the CD8 coreceptor for tumor recognition. (A) CD8α or CD8β expression on clone FE11 cells and FE11 γδTCR–transduced αβ T cells. (B) CD4⁺ and CD8⁺ αβT cells transduced with the FE11 γδTCR were sorted and cocultured with mock (left) and TEG011 (right) target cells. (C) TEG011 T-cell activation was assessed by IFN-γ ELISPOT. CD4⁺ and CD8⁺ αβT cells expressing the FE11 γδTCR were coincubated with SW480 target cells as in panel B, but in the presence of a control antibody or blocking antibodies against CD8α or CD8β. (D) αβT cells were transduced with WT CD8α or a truncated, signaling-deficient CD8α variant (CD8α′), alongside the γδTCR-FE11, after which the CD4⁺, CD8⁺, CD4⁺CD8α⁺, and CD4⁺CD8α′⁺ T-cell populations were sorted. Recognition of healthy PBMCs and SW480 tumor target cells was assessed by measuring IFN-γ secretion using ELISPOT. Error bars represent the standard error of the mean (n ≥ 1). *P < .05; **P < .01; ***P < .001.