Membrane association of the CD3ε signaling domain is required for optimal T cell development and function

J Immunol. 2014 Jul 1;193(1):258-67. doi: 10.4049/jimmunol.1400322. Epub 2014 Jun 4.


The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting T cells, the CD3ε cytoplasmic tail associates with the plasma membrane via a proximal basic-rich stretch (BRS). In this study, we show that mice lacking a functional CD3ε-BRS exhibited substantial reductions in thymic cellularity and limited CD4- CD8- double-negative (DN) 3 to DN4 thymocyte transition, because of enhanced DN4 TCR signaling resulting in increased cell death and TCR downregulation in all subsequent populations. Furthermore, positive, but not negative, T cell selection was affected in mice lacking a functional CD3ε-BRS, which led to limited peripheral T cell function and substantially reduced responsiveness to influenza infection. Collectively, these results indicate that membrane association of the CD3ε signaling domain is required for optimal thymocyte development and peripheral T cell function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD3 Complex / immunology*
  • Cell Membrane / genetics
  • Cell Membrane / immunology*
  • Mice
  • Mice, Knockout
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Thymocytes / cytology
  • Thymocytes / immunology*


  • CD3 Complex
  • Cd3e protein, mouse
  • Receptors, Antigen, T-Cell