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Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes
Author(s) -
Anouk M. F. van der Gracht,
Mark A. R. de Geus,
Marcel Camps,
Tracy J. Ruckwardt,
Alexi J. C. Sarris,
Jessica S. Bremmers,
Elmer Maurits,
Joanna B. Pawlak,
Michelle M. Posthoorn,
Kimberly M. Bonger,
Dmitri V. Filippov,
Herman S. Overkleeft,
Marc S. Robillard,
Ferry Ossendorp,
Sander I. van Kasteren
Publication year - 2018
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.8b00155
Subject(s) - epitope , in vivo , cytotoxic t cell , t cell , chemistry , cell , microbiology and biotechnology , biology , in vitro , biochemistry , antigen , immune system , immunology , genetics
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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