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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
Regulation of Immune Activation by Optical Control of TLR1/2 Heterodimerization
Hong-Guo Hu1, Pu-Guang Chen1, Guanyu Wang2
1Department of Chemistry, Tsinghua University, Key Lab of Bioorganic Phosphorus Chemistry and Chemical Biology, Beijing, 100084, P. R. China.
Abstract:
The activation of toll-like receptors (TLRs) plays important roles in the immune response. The ability to control the activities of TLRs could be usable as a switch for immune response. Here we have rationally designed and synthesized a photoswitchable Pam3 CSK4 derivative-P10-to control the activation of TLR1/2. The ground-state trans-P10 was able to stimulate and activate antigen-presenting cells (APCs) by promoting TLR1/2 heterodimerization. However, cis-P10, derived from UV irradiation of trans-P10, reduced the activities of APCs by impeding the TLR1/2 heterodimerization. In the absence of UV radiation, the cis-P10 slowly returned to its ground trans state, restoring the activities of the APCs stimulation. Our results indicated that optical control of TLR1/2 heterodimerization mediated by the photoswitchable P10 offers the potential to regulate immune activation and inflammation.
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