Designer T cells by T cell receptor replacement

Eur J Immunol. 2006 Nov;36(11):3052-9. doi: 10.1002/eji.200636539.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Transfer Techniques
  • Humans
  • Mice
  • Receptors, Antigen, T-Cell / analysis
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • Tissue Engineering*


  • Receptors, Antigen, T-Cell