T cell‐mediated cytotoxicity: Discrimination between antigen recognition, lethal hit and cytolysis phase

Using a 51Cr release cytotoxicity assay, the cytotoxic effector phase of in vitro activated mouse T lymphocytes (killer cells) against 51Cr‐labeled target cells has been investigated. It is shown that within 5–10 minutes of contact between killer cells and target cells, the target cells are already committed to lysis, therefore, antigen recognition and “lethal hit” must have taken place within this period of time. In contrast, target cell lysis (cytolysis phase) requires up to 3–4 h in order to be completed; it occurs independently of killer cells and it is highly temperature dependent. The killer cell‐dependent phase (antigen‐recognition and “lethal hit”) is dissociated into two consecutive steps. The first step represents a specific and reversible event which takes place both at 4 °C and 37 °C. In contrast, the second step is found to be temperature dependent, but irreversible, and commits the target cells to lysis. It is concluded that the antigen recognition phase takes place during the first step and that the second step represents the “lethal hit” phase.