RT Journal Article
T1 The CD3 Conformational Change in the gd T Cell Receptor Is Not Triggered by Antigens but Can Be Enforced to Enhance Tumor Killing
A1 Dopfer, Elaine P
A1 Hartl, Frederike A
A1 Oberg, Hans-Heinrich
A1 Siegers, Grabrielle M
A1 Yousefi, S. Sascha
A1 Kock, Sylvia
A1 Fiala, Gina J
A1 Garcillán Goyoaga, Beatriz de
A1 Sandstrom, Andrew
A1 Alarcón, Balbino
A1 Regueiro González-Barros, José Ramón
A1 Kabelitz, Dieter
A1 Adams, Erin J
A1 Minguet, Susana
A1 Wesch, Daniela
A1 Fisch, Paul
A1 Schamel, Wolfgang W.A.
AB Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the ab TCR antigen induces a conformational change at the CD3 subunits (CD3 CC) that is absolutely required for abTCR activation. Here, we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse G8 or the human Vg9Vd2 gdTCR. We find that there is a fundamental difference between the activation mechanisms of the abTCR and gdTCR that map to the constant regions of the TCRab/gd heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal anti-CD3 promoted proximal gdTCR signaling but inhibited cytokine secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor cell lysis by activated human gd T cells. Thus, manipulation of the CD3 CC might be exploited to improve clinical gd T cellbased immunotherapies.
PB Elsevier
SN 2211-1247
YR 2014
FD 2014-05-22
LK https://hdl.handle.net/20.500.14352/34397
UL https://hdl.handle.net/20.500.14352/34397
LA eng
NO Unión Europea. FP7
NO Ministerio de Ciencia e Innovación (MICINN)
NO Fundación Ramón Areces
NO German Research Foundation (DFG)
DS Docta Complutense
RD 14 abr 2025