T-cell receptor signal transmission: who gives an ITAM?
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.
Pitcher
Lisa A
LA
Center for Immunology, University of Texas Southwestern Medical Center, Room NA7.201, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.
van Oers
Nicolai S C
NS
D000818:Animals; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine