Abstract
The transporter associated with antigen processing (TAP) is a member of the family of ABC transporters that translocate a large variety of substrates across membranes1. TAP transports peptides from the cytosol into the endoplasmic reticulum for binding to MHC class I molecules and for subsequent presentation to the immune system2. Here we follow the lateral mobility of TAP in living cells. TAP's mobility increases when it is inactive and decreases when it translocates peptides. Because TAP activity is dependent on substrate, the mobility of TAP is used to monitor the intracellular peptide content in vivo. Comparison of the diffusion rates in peptide-free and peptide-saturated cells indicates that normally about one-third of all TAP molecules actively translocate peptides. However, during an acute influenza infection TAP becomes fully employed owing to the production and degradation of viral proteins. Furthermore, TAP activity depends on continuing protein translation. This implies that MHC class I molecules mainly sample peptides that originate from newly synthesized proteins, to ensure rapid presentation to the immune system.
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Acknowledgements
We thank K. Döring, M. van Ham and K. Jalink for discussions, L. Oomen for help with the confocal microscope, R. Wubbolts for support with microinjection, P. Vlottes (ICN Holland) for a sample of ribavirin, and A. Benham and T. Schumacher for critically reading the manuscript.
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Reits, E., Vos, J., Grommé, M. et al. The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404, 774–778 (2000). https://doi.org/10.1038/35008103
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DOI: https://doi.org/10.1038/35008103
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