TAPBPR mediates peptide dissociation from MHC class I using a leucine lever

Abstract
Data availability
Article and author information
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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

The following data sets were generated

1. Ilca FT
2. Neerincx A
3. Hermann C
4. Marcu A
5. Stevanovic S
6. Deane JE
7. Boyle LH
(2018) Data from: TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
Dryad, doi:10.5061/dryad.p5k0156.

https://dx.doi.org/10.5061/dryad.p5k0156

Article and author information

Author details

Florin Tudor Ilca

Department of Pathology, University of Cambridge, Cambridge, United Kingdom

Competing interests
Florin Tudor Ilca, Some aspects of the work included in this manuscript form part of a recent patent application. Applicant: Cambridge Enterprise Limited. Application number: 1801323.5, Status: Pending.

"This ORCID iD identifies the author of this article:" 0000-0002-6582-8007
Andreas Neerincx

Department of Pathology, University of Cambridge, Cambridge, United Kingdom

Competing interests
Andreas Neerincx, Some aspects of the work included in this manuscript form part of a recent patent application. Applicant: Cambridge Enterprise Limited. Application number: 1801323.5, Status: Pending.
Clemens Hermann

Department of Integrative Biomedical Sciences, Division of Chemical and Systems Biology, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

Competing interests
No competing interests declared.
Ana Marcu

Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-0808-8097
Stefan Stefvanovic

Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany

Competing interests
No competing interests declared.
Janet E Deane

Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4863-0330
Louise H Boyle

Department of Pathology, University of Cambridge, Cambridge, United Kingdom

For correspondence
lhb22@cam.ac.uk

Competing interests
Louise H Boyle, Some aspects of the work included in this manuscript form part of a recent patent application. Applicant: Cambridge Enterprise Limited. Application number: 1801323.5, Status: Pending.

"This ORCID iD identifies the author of this article:" 0000-0002-3105-6555

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

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.