Full Activation of the T Cell Receptor Requires Both Clustering and Conformational Changes at CD3

TY - JOUR

T1 - Full Activation of the T Cell Receptor Requires Both Clustering and Conformational Changes at CD3

AU - Minguet, Susana

AU - Swamy, Mahima

AU - Alarcón, Balbino

AU - Luescher, Immanuel F.

AU - Schamel, Wolfgang W.A.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRαβ ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRαβ ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRαβ is transmitted to the CD3 subunits and to the intracellular signaling machinery.

AB - T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRαβ ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRαβ ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRαβ is transmitted to the CD3 subunits and to the intracellular signaling machinery.

KW - MOLIMMUNO

KW - SIGNALING

UR - https://www.scopus.com/pages/publications/33846224785

U2 - 10.1016/j.immuni.2006.10.019

DO - 10.1016/j.immuni.2006.10.019

M3 - Article

C2 - 17188005

AN - SCOPUS:33846224785

SN - 1074-7613

VL - 26

SP - 43

EP - 54

JO - Immunity

JF - Immunity

IS - 1

ER -