Since their discovery, considerable progress has been made in determining how ITAMs initiate signaling cascades and thereby couple their associated receptors to distal effector responses. In this review, we focus on the TCR as a paradigm for ITAM-mediated signal initiation.

An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors, cell-surface proteins found mainly on immune cells. [1]

May 22, 2018 · To address the effect of receptor ITAM multiplicity without perturbing the underlying TCR signaling network, we developed synthetic receptors of varying ITAM multiplicities that responded to drug-mediated ligation and measured the output response at …

Nov 9, 2023 · Here we evaluated the effect of inactivating the three CD3ζ chain ITAMs on TCR signaling and T cell effector responses using a conditional ‘switch’ mouse model.

May 11, 2015 · ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We...

Mar 13, 2007 · The immunoreceptors rely on different ITAM-containing adapter subunits for signaling: The TCR uses primarily the CD3ζ chain, the BCR uses associated immunoglobulin (Ig) α and β chains, the FcRs use mainly the FcRγ chain, and activating NK receptors and TREM1 and 2 rely primarily on DAP12 (Table 1).

Here we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4 − CD8 − double negative (DN) to CD4 + CD8 + (DP) maturation due to low TCR expression and signaling.

2 days ago · Moreover, the mere presence of 3-ITAM CARs on T cells, even in absence of a CAR antigen, produced a somewhat lower TCR-mediated response than 1-ITAM CAR T cells.

Signaling processes are controlled by the ten immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant chains of the TCR complex (TCR ζ and CD3-γ, -δ and -ε). Here, we discuss recent studies of the functions of TCR invariant chains and the contribution of the ten ITAMs to T-cell signal transmission.

May 22, 2018 · Unique among antigen receptors, the TCR complex uses 10 ITAMs to transduce peptide-MHC binding to the cell interior. Using synthetic, drug-inducible receptor-ligand pairs, it was found that greater ITAM multiplicity primarily enhanced the efficiency with which ligand binding was converted into an intracellular signal.