Cell Biology of T Cell Receptor Expression and Regulation

Annu Rev Immunol. 2018 Apr 26;36:103-125. doi: 10.1146/annurev-immunol-042617-053429. Epub 2017 Dec 20.


T cell receptors (TCRs) are protein complexes formed by six different polypeptides. In most T cells, TCRs are composed of αβ subunits displaying immunoglobulin-like variable domains that recognize peptide antigens associated with major histocompatibility complex molecules expressed on the surface of antigen-presenting cells. TCRαβ subunits are associated with the CD3 complex formed by the γ, δ, ε, and ζ subunits, which are invariable and ensure signal transduction. Here, we review how the expression and function of TCR complexes are orchestrated by several fine-tuned cellular processes that encompass (a) synthesis of the subunits and their correct assembly and expression at the plasma membrane as a single functional complex, (b) TCR membrane localization and dynamics at the plasma membrane and in endosomal compartments, (c) TCR signal transduction leading to T cell activation, and (d) TCR degradation. These processes balance each other to ensure efficient T cell responses to a variety of antigenic stimuli while preventing autoimmunity.

Keywords: TCR-CD3; assembly; conformational change; endocytosis; recycling; signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • CD3 Complex / genetics
  • CD3 Complex / metabolism
  • Cell Membrane / metabolism
  • Endocytosis / genetics
  • Endocytosis / immunology
  • Endosomes / metabolism
  • Gene Expression Regulation*
  • Humans
  • Immunomodulation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Proteolysis
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*


  • Biomarkers
  • CD3 Complex
  • Multiprotein Complexes
  • Receptors, Antigen, T-Cell