Significance Human γδ T lymphocytes have innate-like and adaptive-like functions and can circulate in blood or reside in tissues. They are activated by specific antigens recognized by their T-cell receptor and recognize infected and transformed cells, suggesting that cellular stress is involved in specific antigen expression. However, molecular characterization of stress-induced antigens remains elusive, hampering our understanding of the role of γδ T cells in cancer and infections. In the present study we identify annexin A2 as such stress-induced antigen known as a phospholipid-binding protein involved in tumorigenesis, redox potential regulation, and wound healing. Stress-mediated membrane exposure of annexin A2 could thus constitute a danger signal for γδ T cells to recognize various cell dysregulations and protect the host against cancer and infections.