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

ABSTRACT: 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.

SUBMITTER: van der Gracht AMF

PROVIDER: S-EPMC6006443 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

van der Gracht Anouk M F AMF de Geus Mark A R MAR Camps Marcel G M MGM Ruckwardt Tracy J TJ Sarris Alexi J C AJC Bremmers Jessica J Maurits Elmer E Pawlak Joanna B JB Posthoorn Michelle M MM Bonger Kimberly M KM Filippov Dmitri V DV Overkleeft Herman S HS Robillard Marc S MS Ossendorp Ferry F van Kasteren Sander I SI

ACS chemical biology 20180511 6

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 invers ...[more]

PMID: 29733186

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