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

  • 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.

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Author:Markus Braner, Nicole Koller, Julia Knauer, Valentina Herbring, Susanne Hank, Ralph WienekeORCiDGND, Robert TampéORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30881629
Parent Title (English):Chemical science
Place of publication:Cambridge
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/12/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/25
Page Number:5
First Page:2001
Last Page:2005
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0