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Issue 7, 2019
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Optical control of the antigen translocation by synthetic photo-conditional viral inhibitors

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Abstract

The immune system makes use of major histocompatibility complex class I (MHC I) molecules to present peptides to other immune cells, which can evoke an immune response. Within this process of antigen presentation, the MHC I peptide loading complex, consisting of a transporter associated with antigen processing TAP, MHC I, and chaperones, is key to the initiation of immune response by shuttling peptides from the cytosol into the ER lumen. However, it is still enigmatic how the flux of antigens is precisely coordinated in time and space, limiting our understanding of antigen presentation pathways. Here, we report on the development of a synthetic viral TAP inhibitor that can be cleaved by light. This photo-conditional inhibitor shows temporal blockade of TAP-mediated antigen translocation, which is unleashed upon illumination. The recovery of TAP activity was monitored at single-cell resolution both in human immune cell lines and primary cells. The development of a photo-conditional TAP inhibitor thus expands the repertoire of chemical intervention tools for immunological processes.

Graphical abstract: Optical control of the antigen translocation by synthetic photo-conditional viral inhibitors

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Supplementary files

Article information


Submitted
31 Oct 2018
Accepted
15 Dec 2018
First published
17 Dec 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 2001-2005
Article type
Edge Article

Optical control of the antigen translocation by synthetic photo-conditional viral inhibitors

M. Braner, N. Koller, J. Knauer, V. Herbring, S. Hank, R. Wieneke and R. Tampé, Chem. Sci., 2019, 10, 2001
DOI: 10.1039/C8SC04863K

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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