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

Lisa A Pitcher1, Nicolai S C van Oers

  • 1Center for Immunology, University of Texas Southwestern Medical Center, Room NA7.201, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.

Trends in Immunology
|October 14, 2003
PubMed

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.

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