TCR/CD3 coupling to Fas-based cytotoxicity

J Exp Med. 1995 Feb 1;181(2):781-6. doi: 10.1084/jem.181.2.781.


We studied the coupling of the TCR/CD3 complex to a T cell effector function, namely Fas-based T-cell-mediated cytotoxicity. Encounter or re-encounter with antigen was mimicked by treating 5 d mixed lymphocyte culture cells or T cell hybridomas with anti-CD3 antibody. This TCR/CD3 engagement induced swift expression of Fas-based cytotoxicity in these cells. Induction of Fas-based cytotoxicity was Ca(2+)-dependent, while its execution was not; induction was sensitive to macromolecular synthesis inhibitors, in line with a demonstrable increase of the Fas ligand (Fas-L) message. We also used T cell hybridomas transfected with various constructs to dissect the involvement of distinct components of the TCR/CD3 complex. The cytoplasmic domain of the CD3 zeta chain was able to transduce by itself a signal leading to Fas-L expression, unless there were mutations in its activation receptor homology sequence 1 (ARH-1) motifs. On the one hand, these findings are relevant to signal transduction pathways coupled to the TCR/CD3, and on the other hand, to the involvement of Fas-based T cell-mediated cytotoxicity in various physiological and possibly pathophysiological situations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism*
  • CD3 Complex / metabolism*
  • Cytotoxicity, Immunologic*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • fas Receptor


  • Antigens, Surface
  • CD3 Complex
  • Receptors, Antigen, T-Cell
  • fas Receptor