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TAPBPR mediates peptide dissociation from MHC class I using a leucine lever

Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess...

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Detalles Bibliográficos
Autores principales: Ilca, F Tudor, Neerincx, Andreas, Hermann, Clemens, Marcu, Ana, Stevanović, Stefan, Deane, Janet E, Boyle, Louise H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307860/
https://www.ncbi.nlm.nih.gov/pubmed/30484775
http://dx.doi.org/10.7554/eLife.40126
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author Ilca, F Tudor
Neerincx, Andreas
Hermann, Clemens
Marcu, Ana
Stevanović, Stefan
Deane, Janet E
Boyle, Louise H
author_facet Ilca, F Tudor
Neerincx, Andreas
Hermann, Clemens
Marcu, Ana
Stevanović, Stefan
Deane, Janet E
Boyle, Louise H
author_sort Ilca, F Tudor
collection PubMed
description Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediated peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing on MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.
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spelling pubmed-63078602019-01-02 TAPBPR mediates peptide dissociation from MHC class I using a leucine lever Ilca, F Tudor Neerincx, Andreas Hermann, Clemens Marcu, Ana Stevanović, Stefan Deane, Janet E Boyle, Louise H eLife Immunology and Inflammation Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediated peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing on MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity. eLife Sciences Publications, Ltd 2018-11-28 /pmc/articles/PMC6307860/ /pubmed/30484775 http://dx.doi.org/10.7554/eLife.40126 Text en © 2018, Ilca et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Ilca, F Tudor
Neerincx, Andreas
Hermann, Clemens
Marcu, Ana
Stevanović, Stefan
Deane, Janet E
Boyle, Louise H
TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title_full TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title_fullStr TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title_full_unstemmed TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title_short TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
title_sort tapbpr mediates peptide dissociation from mhc class i using a leucine lever
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307860/
https://www.ncbi.nlm.nih.gov/pubmed/30484775
http://dx.doi.org/10.7554/eLife.40126
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