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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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Publication details

The article was received on 31 Oct 2018, accepted on 15 Dec 2018 and first published on 17 Dec 2018


Article type: Edge Article
DOI: 10.1039/C8SC04863K
Citation: Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    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, Advance Article , DOI: 10.1039/C8SC04863K

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