TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway
- University of Cambridge, United Kingdom
- University of Cape Town, South Africa
- University of Southampton, United Kingdom
- University of Aberdeen, United Kingdom
- Eberhard Karls University Tübingen, Germany
Abstract
Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on class I, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide-editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex.
Data availability
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Data from: TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality controlAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
Wellcome (Senior Research Fellowship 104647)
- Andreas Neerincx
- Louise H Boyle
Royal Society (University Research Fellowship,UF100371)
- Janet E Deane
Cancer Research UK (Programme Grant,C7056A)
- Andy van Hateren
- Tim Elliott
Deutsche Forschungsgemeinschaft (SFB 685)
- Nico Trautwein
- Stefan Stevanović
Wellcome (PhD studentship,089563)
- Clemens Hermann
Wellcome (Strategic Award 100140)
- Robin Antrobus
Wellcome (programme grant,WT094847MA)
- Huan Cao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- David H Margulies, National Institutes of Health, United States
Version history
- Received: November 7, 2016
- Accepted: April 14, 2017
- Accepted Manuscript published: April 20, 2017 (version 1)
- Version of Record published: May 23, 2017 (version 2)
Copyright
© 2017, Neerincx 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 bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway
eLife 6:e23049.
https://doi.org/10.7554/eLife.23049
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