Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response

Using a chemically homogeneous radiolabeled peptide of high specific activity (I-125-QLSPYPFDL, 3.5 x 10(18) cpm per mole) we show that at a peptide concentration (5 pM) causing half-maximal lysis of target cells by a cytolytic T lymphocyte (CTL) clone that recognizes the peptide in association with L(d), a class I MHC protein, only 3 peptide molecules on average are bound by L(d) per target cell. From the distribution of L(d) on the target cells, we suggest that a single peptide-MHC complex per target cell can trigger activation of the T cell cytolytic response.