The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing
Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the abTCR, 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...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/660663 |
| Acceso en línea: | http://hdl.handle.net/10486/660663 https://dx.doi.org/10.1016/j.celrep.2014.04.049 |
| Access Level: | acceso abierto |
| Palabra clave: | Combinatorial code Drosophila FMRFa Neuropeptidergic cell identity Temporal genes Terminal differentiation Biología y Biomedicina / Biología |
| Sumario: | Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the abTCR, 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. |
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