Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells
| Autor: | Peter Kufer, Patrick A. Baeuerle, Robert Hofmeister, Sonja Offner, Andrea Romaniuk |
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| Rok vydání: | 2006 |
| Předmět: |
T cell
Immunology CD1 Epitopes T-Lymphocyte Cell Communication Biology Lymphocyte Activation Cell Line Tumor Neoplasms Antibodies Bispecific MHC class I medicine Humans Cytotoxic T cell Antigen-presenting cell Molecular Biology Microscopy Confocal Histocompatibility Antigens Class I CD28 MHC restriction Molecular biology Coculture Techniques Cell biology medicine.anatomical_structure biology.protein Tumor Escape CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Molecular Immunology. 43:763-771 |
| ISSN: | 0161-5890 |
| Popis: | Certain bispecific single-chain antibody constructs exhibit an extraordinary potency for polyclonal T cell engagement and target cell lysis. Here we studied the structural basis for this potency, using laser scanning confocal microscopy. Cytolytic human T cell synapses could be triggered either by addition of a specific peptide antigen or an Ep-CAM-/CD3-bispecific T cell engager (BiTE). Both kinds of synapses showed a comparable distribution of all protein markers investigated. Two other BiTEs constructed from different Ep-CAM-specific antibodies gave similar results. BiTEs could also induce lytic synapses between human T cells and a MHC class I-negative, Ep-CAM cDNA-transfected cell line resulting in potent target cell lysis. This shows that certain T cell recognition molecules on target cells are dispensable for synapse formation and BiTE activity, and suggests that BiTE-activated polyclonal T cells may ignore major immune evasion mechanisms of tumor cells in vivo, such as loss of MHC class I expression. |
| Databáze: | OpenAIRE |
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