TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway
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Authors
Neerincx, A
Hermann, C
Antrobus, R
van Hateren, A
Cao, H
Trautwein, N
Stevanović, S
Elliott, T
Publication Date
2017-04-20Journal Title
eLife
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Volume
6
Number
e23049
Language
English
Type
Article
This Version
VoR
Metadata
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Neerincx, A., Hermann, C., Antrobus, R., van Hateren, A., Cao, H., Trautwein, N., Stevanović, S., et al. (2017). 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
Abstract
Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether 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 that is known to regenerate the Glc$_1$Man$_9$GlcNAc$_2$ 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 MHC class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on MHC class I molecules, 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.
Keywords
HLA, MHC, TAPBPL, TAPBPR, antigen processing & presentation, cell biology, human, immunology
Relationships
Is supplemented by: https://doi.org/10.5061/dryad.8fh3g
Sponsorship
Wellcome Trust (Senior Research Fellowship 104647, PhD studentship,089563, Strategic Award 100140,WT094847MA) , Royal Society (University Research Fellowship,UF100371), Cancer Research UK (Programme Grant C7056A), Deutsche Forschungsgemeinschaft (SFB 685)
Funder references
Royal Society (UF150682)
WELLCOME TRUST (104647/Z/14/Z)
Wellcome Trust (085038/Z/08/Z)
Wellcome Trust (089563/Z/09/Z)
Identifiers
External DOI: https://doi.org/10.7554/eLife.23049
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264969
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International