Designer T cells by T cell receptor replacement


  • D. Sommermeyer
  • J. Neudorfer
  • M. Weinhold
  • M. Leisegang
  • B. Engels
  • E. Noessner
  • M.H. Heemskerk
  • J. Charo
  • D.J. Schendel
  • T. Blankenstein
  • H. Bernhard
  • W. Uckert


  • European Journal of Immunology


  • Eur J Immunol 36 (11): 3052-3059


  • T cell receptor (TCR) gene transfer is a convenient method to produce antigen-specific T cells for adoptive therapy. However, the expression of two TCR in T cells could impair their function or cause unwanted effects by mixed TCR heterodimers. With five different TCR and four different T cells, either mouse or human, we show that some TCR are strong - in terms of cell surface expression - and replace weak TCR on the cell surface, resulting in exchange of antigen specificity. Two strong TCR are co-expressed. A mouse TCR replaces human TCR on human T cells. Even though it is still poorly understood why some TCRalpha/beta combinations are preferentially expressed on T cells, our data suggest that, in the future, designer T cells with exclusive tumor reactivity can be generated by T cell engineering.