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<p>Motivated by experimental observations that T-cells can activate as a consequence of clustering of T-cell receptors, we hypothesize that steric confinement between the intracellular chains of the TCR could play a role. Using coarse-grained simulations, we show that steric interactions between TCRs are sufficient to induce appreciable stretch of the intracellular domains of CD3<InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(\zeta\)</EquationSource> </InlineEquation> chains. We propose a model, in which the difference in membrane distances between the phosphatase CD45 and the kinases lck and fyn is able to sense the clustering-induced CD3<InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(\zeta\)</EquationSource> </InlineEquation> stretch: we estimate a 1.5- to 2-fold increase in phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) at CD3<InlineEquation ID="IEq4"> <EquationSource Format="TEX">\(\zeta\)</EquationSource> </InlineEquation> upon TCR clustering.</p>

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Clustering of the T-cell receptor complex may facilitate T-cell activation by stretching of CD3\(\zeta\) cytoplasmic tails

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Steven Siegl,
  • Sebastian Fürthauer,
  • Gerhard J. Schütz

摘要

Motivated by experimental observations that T-cells can activate as a consequence of clustering of T-cell receptors, we hypothesize that steric confinement between the intracellular chains of the TCR could play a role. Using coarse-grained simulations, we show that steric interactions between TCRs are sufficient to induce appreciable stretch of the intracellular domains of CD3 \(\zeta\) chains. We propose a model, in which the difference in membrane distances between the phosphatase CD45 and the kinases lck and fyn is able to sense the clustering-induced CD3 \(\zeta\) stretch: we estimate a 1.5- to 2-fold increase in phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) at CD3 \(\zeta\) upon TCR clustering.