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: | , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
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The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killingDopfer, Elaine P.Hartl, Frederike A.Oberg, Hans-HeinrichSiegers, Gabrielle M.Yousefi, O. SaschaKock, SylviaFiala, Gina J.Garcillán, BeatrizSandstrom, AndrewAlarcón, BalbinoRegueiro, José R.Kabelitz, DieterAdams, Erin J.Minguet, SusanaWesch, DanielaFisch, PaulSchamel, Wolfgang W.A.Combinatorial codeDrosophilaFMRFaNeuropeptidergic cell identityTemporal genesTerminal differentiationBiología y Biomedicina / BiologíaActivation 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.This work was supported by the German Research Foundation (DFG) through grants SFB620 to W.W.A.S. and P.F., SCHA976/2-1 to W.W.A.S., the Excellence Initiatives GSC-4 (Spemann Graduate School), EXC294 (BIOSS) to G.J.F and W.W.A.S., EXC306 (Inflammation-at-Interfaces) to D.K., the Pancreatic Cancer Consortium Kiel (WE 3559/2-1) to D.W. and D.K., the EU through grant FP7/2007-2013 (SYBILLA) to W.W.A.S., E.P.D., and B.A., the Innovationfonds Forschung-2012 grant to F.A.H. and S.M., MEC (SAF2011-24235) to B.G., and the Fundacion Ramon Areces to B.A.Cell PressDepartamento de Biología MolecularFacultad de Ciencias20142014-06-12research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/660663https://dx.doi.org/10.1016/j.celrep.2014.04.049reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6606632026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| title |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| spellingShingle |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing Dopfer, Elaine P. Combinatorial code Drosophila FMRFa Neuropeptidergic cell identity Temporal genes Terminal differentiation Biología y Biomedicina / Biología |
| title_short |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| title_full |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| title_fullStr |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| title_full_unstemmed |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| title_sort |
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing |
| dc.creator.none.fl_str_mv |
Dopfer, Elaine P. Hartl, Frederike A. Oberg, Hans-Heinrich Siegers, Gabrielle M. Yousefi, O. Sascha Kock, Sylvia Fiala, Gina J. Garcillán, Beatriz Sandstrom, Andrew Alarcón, Balbino Regueiro, José R. Kabelitz, Dieter Adams, Erin J. Minguet, Susana Wesch, Daniela Fisch, Paul Schamel, Wolfgang W.A. |
| author |
Dopfer, Elaine P. |
| author_facet |
Dopfer, Elaine P. Hartl, Frederike A. Oberg, Hans-Heinrich Siegers, Gabrielle M. Yousefi, O. Sascha Kock, Sylvia Fiala, Gina J. Garcillán, Beatriz Sandstrom, Andrew Alarcón, Balbino Regueiro, José R. Kabelitz, Dieter Adams, Erin J. Minguet, Susana Wesch, Daniela Fisch, Paul Schamel, Wolfgang W.A. |
| author_role |
author |
| author2 |
Hartl, Frederike A. Oberg, Hans-Heinrich Siegers, Gabrielle M. Yousefi, O. Sascha Kock, Sylvia Fiala, Gina J. Garcillán, Beatriz Sandstrom, Andrew Alarcón, Balbino Regueiro, José R. Kabelitz, Dieter Adams, Erin J. Minguet, Susana Wesch, Daniela Fisch, Paul Schamel, Wolfgang W.A. |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Biología Molecular Facultad de Ciencias |
| dc.subject.none.fl_str_mv |
Combinatorial code Drosophila FMRFa Neuropeptidergic cell identity Temporal genes Terminal differentiation Biología y Biomedicina / Biología |
| topic |
Combinatorial code Drosophila FMRFa Neuropeptidergic cell identity Temporal genes Terminal differentiation Biología y Biomedicina / Biología |
| description |
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. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2014-06-12 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/660663 https://dx.doi.org/10.1016/j.celrep.2014.04.049 |
| url |
http://hdl.handle.net/10486/660663 https://dx.doi.org/10.1016/j.celrep.2014.04.049 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Cell Press |
| publisher.none.fl_str_mv |
Cell Press |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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