TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Andreas Neerincx; Clemens Hermann; Robin Antrobus; Andy van Hateren; Huan Cao; Nico Trautwein; Stefan Stevanović; Tim Elliott; Janet E. Deane; Louise H. Boyle

doi:10.7554/eLife.23049

TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E. Deane, Louise H. Boyle

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

7 Downloads (Pure)

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.

Original language	English
Article number	e23049
Pages (from-to)	1-25
Number of pages	25
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.23049
Publication status	Published - 20 Apr 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.7554/eLife.23049Licence: CC BY

TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway
© Copyright Neerincx et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 1.85 MBLicence: CC BY

Data from: TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway
Neerincx, A. (Creator), Hermann, C. (Creator), Antrobus, R. (Creator), van Hateren, A. (Creator), Cao, H. (Creator), Trautwein, N. (Creator), Stevanović, S. (Creator), Elliott, T. (Creator), Deane, J. E. (Creator) & Boyle, L. H. (Creator), Dryad Digital Repository, 18 Apr 2018
DOI: 10.5061/dryad.8fh3g
Dataset

Cite this

@article{c1dbe886f82747ea8fe0629680aaa350,

title = "TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway",

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.",

author = "Andreas Neerincx and Clemens Hermann and Robin Antrobus and {van Hateren}, Andy and Huan Cao and Nico Trautwein and Stefan Stevanovi{\'c} and Tim Elliott and Deane, {Janet E.} and Boyle, {Louise H.}",

note = "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 Stevanovi{\'c} Wellcome: PhD studentship, 089563, Clemens Hermann Wellcome: Strategic Award 100140, Robin Antrobus Wellcome: Programme grant, WT094847MA, Huan Cao Acknowledgements We are extremely grateful to Peter Cresswell and Najla Arshad (Yale University School of Medicine, New Haven, CT) for valuable advice, tapasin and TAP-specific antibody reagents, and the recombinant calreticulin proteins. We thank John Trowsdale (University of Cambridge, UK) for his mentorship and critical reading of this manuscript, and Jim Kaufman (University of Cambridge, UK) for useful discussions. We also thank Yi Cao (Cranfield University, UK) for MATLAB programming for densitometry analysis, and Mark Vickers and Sadie Henderson (Scottish National Blood Transfusion Services, UK) for permitting the use of and assistance with the Amersham WB system. The reagent ARP7099 FEC peptide pool was obtained from the Centre for AIDS Reagents, National Institute for Biological Standards and Control (NIBSC), and was donated by the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH.",

year = "2017",

month = apr,

day = "20",

doi = "10.7554/eLife.23049",

language = "English",

volume = "6",

pages = "1--25",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - TAPBPR bridges UDP-glucose

T2 - glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

AU - Neerincx, Andreas

AU - Hermann, Clemens

AU - Antrobus, Robin

AU - van Hateren, Andy

AU - Cao, Huan

AU - Trautwein, Nico

AU - Stevanović, Stefan

AU - Elliott, Tim

AU - Deane, Janet E.

AU - Boyle, Louise H.

N1 - 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 Acknowledgements We are extremely grateful to Peter Cresswell and Najla Arshad (Yale University School of Medicine, New Haven, CT) for valuable advice, tapasin and TAP-specific antibody reagents, and the recombinant calreticulin proteins. We thank John Trowsdale (University of Cambridge, UK) for his mentorship and critical reading of this manuscript, and Jim Kaufman (University of Cambridge, UK) for useful discussions. We also thank Yi Cao (Cranfield University, UK) for MATLAB programming for densitometry analysis, and Mark Vickers and Sadie Henderson (Scottish National Blood Transfusion Services, UK) for permitting the use of and assistance with the Amersham WB system. The reagent ARP7099 FEC peptide pool was obtained from the Centre for AIDS Reagents, National Institute for Biological Standards and Control (NIBSC), and was donated by the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH.

PY - 2017/4/20

Y1 - 2017/4/20

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.23049

DO - 10.7554/eLife.23049

M3 - Article

C2 - 28425917

VL - 6

SP - 1

EP - 25

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e23049

ER -

TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Abstract

UN SDGs

Access to Document

Fingerprint

Datasets

Data from: TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Cite this