Abstract
Abstract Cytotoxic T lymphocytes (CTL) possess a unique ability to destroy virus-infected cells by releasing cytolytic granules that upon delivery to target cells induce apoptosis. It has been proved that perhaps even a single peptide presented on a target cell renders this cell susceptible for killing by CTL. Using a novel biosensor containing quantum dots (QD) carrying controlled number of cognate and non-cognate peptide-MHC (pMHC) proteins, we have shown that pMHC attached to QD cooperate and that the presence of a single cognate pMHC with all others being non-cognate is sufficient to induce a robust CTL response. To understand how triggering of CTL response leads to delivery of effective lethal hit to target cells, we examined granule polarization and release as well as segregation of immune receptors at interface between CTL and planar bilayer containing cognate pMHC and ICAM-1. We show that exceptionally tight ring junction formed at CTL-bilayer interface functions as a gasket precluding granule escape, which are concentrated in the secretory domain of immunological synapse. We propose that efficient target cell lysis requires 2 essential manipulations of cytolytic granules: release and effective targeting.
Published Version
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