T-cell receptor signal transmission: who gives an ITAM?

Trends Immunol. 2003 Oct;24(10):554-60. doi: 10.1016/j.it.2003.08.003.


T cells have an amazing ability to discern and differentially respond to MHC-embedded peptides that can differ by only a single amino acid. This potential involves a combination of the precise ligand-binding specificities of the T-cell receptor (TCR) and the distinct intracellular signaling processes it transmits. Signaling processes are controlled by the ten immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant chains of the TCR complex (TCR zeta and CD3-gamma, -delta and -epsilon ). Here, we discuss recent studies of the functions of TCR invariant chains and the contribution of the ten ITAMs to T-cell signal transmission. We incorporate these results into two non-exclusive models of TCR signal transduction: the ITAM multiplicity model, which describes a functional redundancy within the TCR zeta and CD3 ITAMs; and the differential signaling model, which proposes distinct functions for the CD3-gamma, -delta and -epsilon and TCR zeta modules.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunity, Cellular / physiology*
  • Lymphocyte Activation / physiology*
  • Receptor-CD3 Complex, Antigen, T-Cell / physiology
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / immunology*
  • Tyrosine / metabolism


  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • Tyrosine