1. Biochemistry and Chemical Biology
  2. Immunology and Inflammation
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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
Research Article
  • Cited 4
  • Views 1,003
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Cite this article as: eLife 2020;9:e55326 doi: 10.7554/eLife.55326

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.

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

Publication 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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