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


Editor's Summary

Must Change Shape
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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{beta}-arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism.
E. Fernandez-Arenas, E. Calleja, N. Martinez-Martin, S. I. Gharbi, R. Navajas, N. Garcia-Medel, P. Penela, A. Alcami, F. Mayor Jr, J. P. Albar, et al. (2014)
EMBO J. 33, 559-577
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Cutting Edge: Evidence for a Dynamically Driven T Cell Signaling Mechanism.
W. F. Hawse, M. M. Champion, M. V. Joyce, L. M. Hellman, M. Hossain, V. Ryan, B. G. Pierce, Z. Weng, and B. M. Baker (2012)
J. Immunol. 188, 5819-5823
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T Cell Receptors are Structures Capable of Initiating Signaling in the Absence of Large Conformational Rearrangements.
R. A. Fernandes, D. A. Shore, M. T. Vuong, C. Yu, X. Zhu, S. Pereira-Lopes, H. Brouwer, J. A. Fennelly, C. M. Jessup, E. J. Evans, et al. (2012)
J. Biol. Chem. 287, 13324-13335
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T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clusters.
B. N. Manz, B. L. Jackson, R. S. Petit, M. L. Dustin, and J. Groves (2011)
PNAS 108, 9089-9094
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Receptors, Signaling Networks, and Disease.
N. Cuesta, N. B. Martin-Cofreces, C. Murga, and H. M. van Santen (2011)
Science Signaling 4, mr3
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Evidence for a functional sidedness to the {alpha}{beta}TCR.
M. S. Kuhns, A. T. Girvin, L. O. Klein, R. Chen, K. D. C. Jensen, E. W. Newell, J. B. Huppa, B. F. Lillemeier, M. Huse, Y.-h. Chien, et al. (2010)
PNAS 107, 5094-5099
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