TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
- University of Cambridge, United Kingdom
- University of Cape Town, South Africa
- University of Tübingen, Germany
Abstract
Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules, however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediate peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing of MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files regarding the lists of peptides presented on MHC class I have been provided for Figures 5
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Data from: TAPBPR mediates peptide dissociation from MHC class I using a leucine leverDryad, doi:10.5061/dryad.p5k0156.
Article and author information
Author details
Funding
Wellcome (104647/Z/14/Z)
- Andreas Neerincx
- Louise H Boyle
South African Medical Research Council
- Clemens Hermann
Royal Society (UF100371)
- Janet E Deane
Bosch-Forschungsstiftung
- Ana Marcu
- Stefan Stefvanovic
Wellcome (109076/Z/15/A)
- Florin Tudor Ilca
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Ilca et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
eLife 7:e40126.
https://doi.org/10.7554/eLife.40126
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