1. Cell Biology
  2. Immunology and Inflammation

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

  1. Andreas Neerincx
  2. Clemens Hermann
  3. Robin Antrobus
  4. Andy van Hateren
  5. Huan Cao
  6. Nico Trautwein
  7. Stefan Stevanović
  8. Tim Elliott
  9. Janet E Deane
  10. Louise H Boyle  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Cape Town, South Africa
  3. University of Southampton, United Kingdom
  4. University of Aberdeen, United Kingdom
  5. Eberhard Karls University Tübingen, Germany
https://doi.org/10.7554/eLife.23049
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  1. Andreas Neerincx
  2. Clemens Hermann
  3. Robin Antrobus
  4. Andy van Hateren
  5. Huan Cao
  6. Nico Trautwein
  7. Stefan Stevanović
  8. Tim Elliott
  9. Janet E Deane
  10. Louise H Boyle
(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
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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.

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Author details

  1. Andreas Neerincx

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. 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
    The authors declare that no competing interests exist.

  3. Robin Antrobus

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Andy van Hateren

    Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3915-0239

  5. Huan Cao

    Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Nico Trautwein

    Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  7. Stefan Stevanović

    Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  8. Tim Elliott

    Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  9. Janet E Deane

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4863-0330

  10. Louise H Boyle

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    lhb22@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3105-6555

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.

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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  1. Andreas Neerincx
  2. Clemens Hermann
  3. Robin Antrobus
  4. Andy van Hateren
  5. Huan Cao
  6. Nico Trautwein
  7. Stefan Stevanović
  8. Tim Elliott
  9. Janet E Deane
  10. Louise H Boyle
(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

Share this article

https://doi.org/10.7554/eLife.23049

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