Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes.
Anouk M F van der GrachtMark A R de GeusMarcel G M CampsTracy J RuckwardtAlexi J C SarrisJessica BremmersElmer MauritsJoanna B PawlakMichelle M PosthoornKimberly M BongerDmitri V FilippovHerman S OverkleeftMarc S RobillardFerry OssendorpSander Izaäk van KasterenPublished in: ACS chemical biology (2018)
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.