Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes

[Image: see text] Activation of a cytotoxic T-cell is a complex multistep process, and tools to study the molecular events and their dynamics that result in T-cell activation in situ and in vivo are scarce. Here, we report the design and use of conditional epitopes for time-controlled T-cell activat...

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Autores principales: van der Gracht, Anouk M. F., de Geus, Mark A. R., Camps, Marcel G. M., Ruckwardt, Tracy J., Sarris, Alexi J. C., Bremmers, Jessica, Maurits, Elmer, Pawlak, Joanna B., Posthoorn, Michelle M., Bonger, Kimberly M., Filippov, Dmitri V., Overkleeft, Herman S., Robillard, Marc S., Ossendorp, Ferry, van Kasteren, Sander I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006443/
https://www.ncbi.nlm.nih.gov/pubmed/29733186
http://dx.doi.org/10.1021/acschembio.8b00155
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author van der Gracht, Anouk M. F.
de Geus, Mark A. R.
Camps, Marcel G. M.
Ruckwardt, Tracy J.
Sarris, Alexi J. C.
Bremmers, Jessica
Maurits, Elmer
Pawlak, Joanna B.
Posthoorn, Michelle M.
Bonger, Kimberly M.
Filippov, Dmitri V.
Overkleeft, Herman S.
Robillard, Marc S.
Ossendorp, Ferry
van Kasteren, Sander I.
author_facet van der Gracht, Anouk M. F.
de Geus, Mark A. R.
Camps, Marcel G. M.
Ruckwardt, Tracy J.
Sarris, Alexi J. C.
Bremmers, Jessica
Maurits, Elmer
Pawlak, Joanna B.
Posthoorn, Michelle M.
Bonger, Kimberly M.
Filippov, Dmitri V.
Overkleeft, Herman S.
Robillard, Marc S.
Ossendorp, Ferry
van Kasteren, Sander I.
author_sort van der Gracht, Anouk M. F.
collection PubMed
description [Image: see text] Activation of a cytotoxic T-cell is a complex multistep process, and tools to study the molecular events and their dynamics that result in T-cell activation in situ and in vivo are scarce. Here, we report the design and use of conditional epitopes for time-controlled T-cell activation in vivo. We show that trans-cyclooctene-protected SIINFEKL (with the lysine amine masked) is unable to elicit the T-cell response characteristic for the free SIINFEKL epitope. Epitope uncaging by means of an inverse-electron demand Diels–Alder (IEDDA) event restored T-cell activation and provided temporal control of T-cell proliferation in vivo.
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spelling pubmed-60064432018-06-20 Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes van der Gracht, Anouk M. F. de Geus, Mark A. R. Camps, Marcel G. M. Ruckwardt, Tracy J. Sarris, Alexi J. C. Bremmers, Jessica Maurits, Elmer Pawlak, Joanna B. Posthoorn, Michelle M. Bonger, Kimberly M. Filippov, Dmitri V. Overkleeft, Herman S. Robillard, Marc S. Ossendorp, Ferry van Kasteren, Sander I. ACS Chem Biol [Image: see text] Activation of a cytotoxic T-cell is a complex multistep process, and tools to study the molecular events and their dynamics that result in T-cell activation in situ and in vivo are scarce. Here, we report the design and use of conditional epitopes for time-controlled T-cell activation in vivo. We show that trans-cyclooctene-protected SIINFEKL (with the lysine amine masked) is unable to elicit the T-cell response characteristic for the free SIINFEKL epitope. Epitope uncaging by means of an inverse-electron demand Diels–Alder (IEDDA) event restored T-cell activation and provided temporal control of T-cell proliferation in vivo. American Chemical Society 2018-05-07 2018-06-15 /pmc/articles/PMC6006443/ /pubmed/29733186 http://dx.doi.org/10.1021/acschembio.8b00155 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle van der Gracht, Anouk M. F.
de Geus, Mark A. R.
Camps, Marcel G. M.
Ruckwardt, Tracy J.
Sarris, Alexi J. C.
Bremmers, Jessica
Maurits, Elmer
Pawlak, Joanna B.
Posthoorn, Michelle M.
Bonger, Kimberly M.
Filippov, Dmitri V.
Overkleeft, Herman S.
Robillard, Marc S.
Ossendorp, Ferry
van Kasteren, Sander I.
Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title_full Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title_fullStr Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title_full_unstemmed Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title_short Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
title_sort chemical control over t-cell activation in vivo using deprotection of trans-cyclooctene-modified epitopes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006443/
https://www.ncbi.nlm.nih.gov/pubmed/29733186
http://dx.doi.org/10.1021/acschembio.8b00155
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