Adequate synapse formation between leukemic B cells and effector T cells following stimulation with artificial TCR ligands

Artificial T cell receptor (TCR) ligands can be used to direct virus-specific cytotoxic T lymphocytes (CTL) towards tumor cells. Because of their size, these constructs may differ from cognate peptides in their ability to induce T cell activation. We here analysed signalling outcomes upon synapse formation between human cytomegalovirus (CMV)-specific CTL and chronic lymphocytic leukemia (CLL) cells through targeted complexes (TC) containing anti-CD20 single-chain variable fragment and biotinylated major histocompatibility complex class I molecules presenting peptides from CMVpp65. TC coated CLL cells were effectively lysed by CMVpp65-specific CTL but induced less interferon gamma (IFN-γ) production than peptide loaded targets. Confocal microscopy revealed that TC induced a redistribution of TCR/CD3 but not CD2 towards the immunological synapse. Furthermore, morphological examination of immunological synapses showed smaller and ‘patchy’ interactions between TC coated B cells and CTL as compared with peptid...