A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor

  1. Lina Sagert
  2. Felix Hennig
  3. Christoph Thomas  Is a corresponding author
  4. Robert Tampé  Is a corresponding author
  1. Goethe-University Frankfurt, Germany

Abstract

Adaptive immunity vitally depends on major histocompatibility complex class I (MHC I) molecules loaded with peptides. Selective loading of peptides onto MHC I, referred to as peptide editing, is catalyzed by tapasin and the tapasin-related TAPBPR. An important catalytic role has been ascribed to a structural feature in TAPBPR called the scoop loop, but the exact function of the scoop loop remains elusive. Here, using a reconstituted system of defined peptide-exchange components including human TAPBPR variants, we uncover a substantial contribution of the scoop loop to the stability of the MHC I-chaperone complex and to peptide editing. We reveal that the scoop loop of TAPBPR functions as an internal peptide surrogate in peptide-depleted environments stabilizing empty MHC I and impeding peptide rebinding. The scoop loop thereby acts as an additional selectivity filter in shaping the repertoire of presented peptide epitopes and the formation of a hierarchical immune response.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Lina Sagert

    Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Felix Hennig

    Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Christoph Thomas

    Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany
    For correspondence
    C.Thomas@em.uni-frankfurt.de
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert Tampé

    Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany
    For correspondence
    tampe@em.uni-frankfurt.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0403-2160

Funding

European Commission (ERC_AdG 789121)

  • Robert Tampé

Deutsche Forschungsgemeinschaft (TA 157/12-1)

  • Robert Tampé

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Pamela J Bjorkman, California Institute of Technology, United States

Version history

  1. Received: January 20, 2020
  2. Accepted: March 12, 2020
  3. Accepted Manuscript published: March 13, 2020 (version 1)
  4. Version of Record published: April 2, 2020 (version 2)

Copyright

© 2020, Sagert 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. Lina Sagert
  2. Felix Hennig
  3. Christoph Thomas
  4. Robert Tampé
(2020)
A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor
eLife 9:e55326.
https://doi.org/10.7554/eLife.55326

Share this article

https://doi.org/10.7554/eLife.55326

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