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Sci. Signal., 11 August 2009
Vol. 2, Issue 83, p. ra43
[DOI: 10.1126/scisignal.2000402]

RESEARCH ARTICLES

Cooperativity Between T Cell Receptor Complexes Revealed by Conformational Mutants of CD3{varepsilon}

Nuria Martínez-Martín1*, Ruth M. Risueño1*, Antonio Morreale2*, Irene Zaldívar1, Elena Fernández-Arenas1, Fernando Herranz2, Angel R. Ortiz2{dagger}, and Balbino Alarcón1{ddagger}

1 Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
2 Bioinformatics Unit, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.

* These authors contributed equally to this work.

{dagger} Deceased 5 May 2008.

Abstract: The CD3{varepsilon} 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 CD3{varepsilon} 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 CD3{varepsilon} subunits. These results emphasize the importance of the conformational change in CD3{varepsilon} for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.

{ddagger} To whom correspondence should be addressed. E-mail: balarcon{at}cbm.uam.es

Citation: N. Martínez-Martín, R. M. Risueño, A. Morreale, I. Zaldívar, E. Fernández-Arenas, F. Herranz, A. R. Ortiz, B. Alarcón, Cooperativity Between T Cell Receptor Complexes Revealed by Conformational Mutants of CD3{varepsilon}. Sci. Signal. 2, ra43 (2009).

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