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 journalArticle

17 Citations (Scopus)
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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 languageEnglish
Article numbere23049
Pages (from-to)1-25
Number of pages25
JournaleLife
Volume6
DOIs
Publication statusPublished - 20 Apr 2017

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Antigen Presentation
Quality Control
Quality control
Antigens
Peptides
Calreticulin
Molecules
Calnexin
mannosylglycoprotein 1,3-glucosyltransferase
Polysaccharides
Cysteine
Glycoproteins
Catalysts
Sensors

Cite this

TAPBPR bridges UDP-glucose : glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway. / Neerincx, Andreas; Hermann, Clemens; Antrobus, Robin; van Hateren, Andy; Cao, Huan; Trautwein, Nico; Stevanović, Stefan; Elliott, Tim; Deane, Janet E.; Boyle, Louise H.

In: eLife, Vol. 6, e23049, 20.04.2017, p. 1-25.

Research output: Contribution to journalArticle

Neerincx, A, Hermann, C, Antrobus, R, van Hateren, A, Cao, H, Trautwein, N, Stevanović, S, Elliott, T, Deane, JE & Boyle, LH 2017, 'TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway', eLife, vol. 6, e23049, pp. 1-25. https://doi.org/10.7554/eLife.23049
Neerincx, Andreas ; Hermann, Clemens ; Antrobus, Robin ; van Hateren, Andy ; Cao, Huan ; Trautwein, Nico ; Stevanović, Stefan ; Elliott, Tim ; Deane, Janet E. ; Boyle, Louise H. / TAPBPR bridges UDP-glucose : glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway. In: eLife. 2017 ; Vol. 6. pp. 1-25.
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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 Stevanović 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 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.",
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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

VL - 6

SP - 1

EP - 25

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e23049

ER -