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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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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. |
format | Online Article Text |
id | pubmed-6307860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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