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Updated: Jun 21, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
Cooperativity between T cell receptor complexes revealed by conformational mutants of CD3epsilon
Nuria Martínez-Martín1, Ruth M Risueño, Antonio Morreale
1Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
Abstract:
The CD3epsilon subunit of the T cell receptor (TCR) complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. To study this process, we built a molecular dynamics model of the transmission of the conformational change within the ectodomains of CD3. The model showed that the CD3 dimers underwent a stiffening effect that was funneled to the base of the CD3epsilon subunit. Mutation of two relevant amino acid residues blocked transmission of the conformational change and the differentiation and activation of T cells. Furthermore, this inhibition occurred even in the presence of excess endogenous CD3epsilon subunits. These results emphasize the importance of the conformational change in CD3epsilon for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.
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