Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells

Mol Immunol. 2006 Feb;43(6):763-71. doi: 10.1016/j.molimm.2005.03.007. Epub 2005 Apr 26.


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.

MeSH terms

  • Antibodies, Bispecific / chemistry
  • Antibodies, Bispecific / immunology*
  • Cell Communication / immunology
  • Cell Line, Tumor
  • Coculture Techniques
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class I*
  • Humans
  • Lymphocyte Activation / immunology
  • Microscopy, Confocal
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Escape


  • Antibodies, Bispecific
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I