T-cell and B-cell Immunology Open access Peer reviewed

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

Steven Siegl, Sebastian Fürthauer, Gerhard J. Schuetz

European Biophysics Journal | Jul 27, 2026

Abstract

Abstract

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 CD3ζ 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 CD3ζ stretch: we estimate a 1.5- to 2-fold increase in phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) at CD3ζ upon TCR clustering.

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Authors

Researchers on this paper

Steven Siegl

first | TU Wien

Sebastian Fürthauer

middle | TU Wien | ORCID 0000-0001-9581-5963

Gerhard J. Schuetz

last | TU Wien | ORCID 0000-0003-1542-1089

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Citation

BibTeX

@article{Siegl2026Clustering,
  title = {Clustering of the T-cell receptor complex may facilitate T-cell activation by stretching of CD3$$\\zeta$$ cytoplasmic tails},
  author = {Steven Siegl and Sebastian Fürthauer and Gerhard J. Schuetz},
  journal = {European Biophysics Journal},
  year = {2026},
  doi = {10.1007/s00249-026-01861-4},
  url = {https://doi.org/10.1007/s00249-026-01861-4}
}

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