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

RESEARCH ARTICLES

Editor's Summary

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The T cell antigen receptor (TCR) complex consists of the TCR {alpha}β subunits noncovalently associated with the {delta}, {varepsilon}, {gamma}, and {zeta} subunits of CD3. Engagement of the TCR by peptide bound to the major histocompatibility complex (MHC) on the surface of an antigen-presenting cell triggers the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the CD3 subunits, and these motifs recruit the proteins that mediate TCR signaling. With a molecular dynamics model, Martínez-Martín et al. investigated how extracellular binding of antigen to the TCR is transduced to the inside of the cell. They identified two residues in CD3{varepsilon} that were critical for the transmission of ligand-induced conformational changes to the intracellular portions of this subunit. CD3{varepsilon} subunits with mutations in either of these residues blocked transmission of the conformational change, and one of these variants functioned as a dominant-negative inhibitor of TCR signaling and T cell activation even when present at very low abundance. The authors propose that the initial interaction of an antigen with a TCR may influence the conformation of oligomeric TCR complexes so that TCRs act cooperatively to transmit signals from peptide-MHC.

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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