Evidence that a Single Peptide?MHC Complex on a Target Cell Can Elicit a Cytolytic T Cell Response (original) (raw)

Research peptide-MHC reaction; and the total number of accessible (functionally empty) MHC binding sites per cell. Al-and Department of Biology Massachusetts Institute of Technology though this approach can be considered to yield only approximate values, it suggested that the epitope densi-Cambridge, Massachusetts 02139 ties required for half-maximal cytolytic responses by cytotoxic T lymphocytes (CTLs) varied from several thousand pepMHC complexes per target cell to fewer Summary than ten with different combinations of MHC proteins, peptides, and CTLs . In addition, Using a chemically homogeneous radiolabeled peptwo independent models for T cell-target cell interactide of high specific activity ( 125 I-QLSPYPFDL, 3.5 ؋ tions have proposed that activation of a T cell can be 10 18 cpm per mole) we show that at a peptide conceninitiated by 3-5 pepMHC complexes (Brower et al., 1994) tration (5 pM) causing half-maximal lysis of target cells or by fewer than 10 complexes per target cell (Sykulev by a cytolytic T lymphocyte (CTL) clone that recoget al., 1995). nizes the peptide in association with L d , a class I MHC The low values are of interest because, if correct, they protein, only 3 peptide molecules on average are focus attention on a critical question concerning the bound by L d per target cell. From the distribution of physiologic activation of T cells: whether T cell triggering L d on the target cells, we suggest that a single peptideinvolves cross-linking TCR molecules, or whether acti-MHC complex per target cell can trigger activation of vation occurs by perturbation of a TCR-multimolecthe T cell cytolytic response. ular complex by a single MHC-peptide (Williams and Beyers , 1992). Accordingly, we have sought to determine whether the low values previously suggested by indirect approaches and reliance on models can be verified by measuring directly the number of peptide mole-

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