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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/40126 |
| _version_ | 1811201278931369984 |
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| author | F Tudor Ilca Andreas Neerincx Clemens Hermann Ana Marcu Stefan Stevanović Janet E Deane Louise H Boyle |
| author_facet | F Tudor Ilca Andreas Neerincx Clemens Hermann Ana Marcu Stefan Stevanović Janet E Deane Louise H Boyle |
| author_sort | F Tudor Ilca |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:19:25Z |
| format | Article |
| id | doaj.art-d267f215987a4db2b173a8b9f985aef6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:19:25Z |
| publishDate | 2018-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d267f215987a4db2b173a8b9f985aef62022-12-22T03:52:10ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.40126TAPBPR mediates peptide dissociation from MHC class I using a leucine leverF Tudor Ilca0https://orcid.org/0000-0002-6582-8007Andreas Neerincx1https://orcid.org/0000-0002-6902-5383Clemens Hermann2https://orcid.org/0000-0002-0009-9501Ana Marcu3https://orcid.org/0000-0003-0808-8097Stefan Stevanović4https://orcid.org/0000-0003-1954-7762Janet E Deane5https://orcid.org/0000-0002-4863-0330Louise H Boyle6https://orcid.org/0000-0002-3105-6555Department of Pathology, University of Cambridge, Cambridge, United KingdomDepartment of Pathology, University of Cambridge, Cambridge, United KingdomDepartment of Integrative Biomedical Sciences, Division of Chemical and Systems Biology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, GermanyDepartment of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany; DKFZ Partner Site Tübingen, German Cancer Consortium, Tübingen, GermanyCambridge Institute for Medical Research, University of Cambridge, Cambridge, United KingdomDepartment of Pathology, University of Cambridge, Cambridge, United KingdomTapasin 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.https://elifesciences.org/articles/40126antigen processingantigen presentationmajor histocompatibility complexTAPBPR/TAPBPL |
| spellingShingle | F Tudor Ilca Andreas Neerincx Clemens Hermann Ana Marcu Stefan Stevanović Janet E Deane Louise H Boyle TAPBPR mediates peptide dissociation from MHC class I using a leucine lever eLife antigen processing antigen presentation major histocompatibility complex TAPBPR/TAPBPL |
| 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 | antigen processing antigen presentation major histocompatibility complex TAPBPR/TAPBPL |
| url | https://elifesciences.org/articles/40126 |
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