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

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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.

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

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Lina Sagert

Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany

Competing interests
The authors declare that no competing interests exist.
Felix Hennig

Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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.

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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.