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

Gracht, A.M.F. van der; Geus, M.A.R. de; Camps, M.G.M.; Ruckwardt, T.J.; Sarris, A.J.C.; Bremmers, J.S.; ... ; Kasteren, S.I. van (2018)

Article / Letter to editor

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.

• All authors: Gracht, A.M.F. van der; Geus, M.A.R. de; Camps, M.G.M.; Ruckwardt, T.J.; Sarris, A.J.C.; Bremmers, J.S.; Maurits, E.; Pawlak, J.B.; Posthoorn, M.M.; Bonger, K.M.; Filippov, D.V.; Overkleeft, H.S.; Robillard, M.S.; Ossendorp, F.A.; Kasteren, S.I. van
• Date: 2018-06-30
• Journal: ACS Chemical Biology
• Volume: 13
• Issue: 6
• Pages: 1569 - 1576
• DOI: doi:10.1021/acschembio.8b00155
• Grant number: ERC-2014-StG-639005