Research ArticleImmunology

Cooperativity Between T Cell Receptor Complexes Revealed by Conformational Mutants of CD3ɛ

Sci. Signal.  11 Aug 2009:
Vol. 2, Issue 83, pp. ra43
DOI: 10.1126/scisignal.2000402

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The CD3ɛ 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 CD3ɛ 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 CD3ɛ subunits. These results emphasize the importance of the conformational change in CD3ɛ for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.

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