Insights into the initiation of TCR signaling

Nat Immunol. 2014 Sep;15(9):798-807. doi: 10.1038/ni.2940.


The initiation of T cell antigen receptor signaling is a key step that can result in T cell activation and the orchestration of an adaptive immune response. Early events in T cell receptor signaling can distinguish between agonist and endogenous ligands with exquisite selectivity, and show extraordinary sensitivity to minute numbers of agonists in a sea of endogenous ligands. We review our current knowledge of models and crucial molecules that aim to provide a mechanistic explanation for these observations. Building on current understanding and a discussion of unresolved issues, we propose a molecular model for initiation of T cell receptor signaling that may serve as a useful guide for future studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptive Immunity / immunology*
  • Humans
  • Lymphocyte Activation / immunology*
  • Major Histocompatibility Complex / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*


  • Receptors, Antigen, T-Cell