DIFFERENT RESPONSES ARE ELICITED IN CYTOTOXIC T-LYMPHOCYTES BY DIFFERENT LEVELS OF T-CELL RECEPTOR OCCUPANCY

We have investigated the level of TCR occupancy required to elicit dif ferent biological responses in human CTL clones specific for an influe nza matrix peptide. Specific cytotoxicity could be detected at extreme ly low peptide concentrations (10(-12) to 10(-15) M). However, IFN-gam ma production, responsiveness to IL-2 and Ca++ fluxes were observed on ly at peptide concentrations >10(-9) M, while autonomous proliferation required even higher peptide concentrations. In parallel experiments we measured TCR downregulation to estimate the number of TCRs triggere d. We observed that at low peptide concentrations, where only cytotoxi city is triggered, TCR downregulation was hardly detectable. Conversel y, induction of IFN-gamma production and proliferation required trigge ring of at least 20-50% of TCRs. Taken together these results indicate that a single CTL can graduate different biological responses as a fu nction of antigen concentration and that killing of the specific targe t does not necessarily result in full activation.