Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density

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Science Signaling  22 May 2018:
Vol. 11, Issue 531, eaan1088
DOI: 10.1126/scisignal.aan1088

ITAM abundance increases receptor potency

T cells transduce extracellular signals by phosphorylating immunoreceptor tyrosine-based activation motifs (ITAMs) within the T cell receptor complex. Why this complex contains more ITAMs than any other immune receptor remains unclear. James engineered drug-responsive synthetic receptors that varied in ITAM abundance to determine how ITAM frequency influenced T cell signaling at the single-cell level. The experimental data fit computational models predicting that increasing ITAM number influenced the efficiency of signal transduction, but not the signal amplitude. Application of these results to human CAR–T cells identified strategies to improve the specificity of these cancer therapeutics.

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