Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR
Summary: Understanding how peptide selection is controlled on different major histocompatibility complex class I (MHC I) molecules is pivotal for determining how variations in these proteins influence our predisposition to infectious diseases, cancer, and autoinflammatory conditions. Although the in...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719312719 |
| _version_ | 1818108157418799104 |
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| author | F. Tudor Ilca Linnea Z. Drexhage Gemma Brewin Sarah Peacock Louise H. Boyle |
| author_facet | F. Tudor Ilca Linnea Z. Drexhage Gemma Brewin Sarah Peacock Louise H. Boyle |
| author_sort | F. Tudor Ilca |
| collection | DOAJ |
| description | Summary: Understanding how peptide selection is controlled on different major histocompatibility complex class I (MHC I) molecules is pivotal for determining how variations in these proteins influence our predisposition to infectious diseases, cancer, and autoinflammatory conditions. Although the intracellular chaperone TAPBPR edits MHC I peptides, it is unclear which allotypes are subjected to TAPBPR-mediated peptide editing. Here, we examine the ability of 97 different human leukocyte antigen (HLA) class I allotypes to interact with TAPBPR. We reveal a striking preference of TAPBPR for HLA-A, particularly for supertypes A2 and A24, over HLA-B and -C molecules. We demonstrate that the increased propensity of these HLA-A molecules to undergo TAPBPR-mediated peptide editing is determined by molecular features of the HLA-A F pocket, specifically residues H114 and Y116. This work reveals that specific polymorphisms in MHC I strongly influence their susceptibility to chaperone-mediated peptide editing, which may play a significant role in disease predisposition. : Ilca et al. explore which human leukocyte antigen class I allotypes are subjected to TAPBPR-mediated peptide editing, revealing TAPBPR has preference for HLA-A, particularly for supertypes A2 and A24, over HLA-B and -C molecules. Keywords: MHC, HLA, polymorphism, TAPBPR/TAPBPL, antigen processing and presentation |
| first_indexed | 2024-12-11T02:10:54Z |
| format | Article |
| id | doaj.art-eca1794479964c7690a001cdde7da6d6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T02:10:54Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-eca1794479964c7690a001cdde7da6d62022-12-22T01:24:16ZengElsevierCell Reports2211-12472019-11-0129616211632.e3Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPRF. Tudor Ilca0Linnea Z. Drexhage1Gemma Brewin2Sarah Peacock3Louise H. Boyle4Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UKFaculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104 Freiburg, GermanyTissue Typing Laboratory, Box 209, Level 6 ATC, Cambridge University Hospitals, NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UKTissue Typing Laboratory, Box 209, Level 6 ATC, Cambridge University Hospitals, NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UKDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Corresponding authorSummary: Understanding how peptide selection is controlled on different major histocompatibility complex class I (MHC I) molecules is pivotal for determining how variations in these proteins influence our predisposition to infectious diseases, cancer, and autoinflammatory conditions. Although the intracellular chaperone TAPBPR edits MHC I peptides, it is unclear which allotypes are subjected to TAPBPR-mediated peptide editing. Here, we examine the ability of 97 different human leukocyte antigen (HLA) class I allotypes to interact with TAPBPR. We reveal a striking preference of TAPBPR for HLA-A, particularly for supertypes A2 and A24, over HLA-B and -C molecules. We demonstrate that the increased propensity of these HLA-A molecules to undergo TAPBPR-mediated peptide editing is determined by molecular features of the HLA-A F pocket, specifically residues H114 and Y116. This work reveals that specific polymorphisms in MHC I strongly influence their susceptibility to chaperone-mediated peptide editing, which may play a significant role in disease predisposition. : Ilca et al. explore which human leukocyte antigen class I allotypes are subjected to TAPBPR-mediated peptide editing, revealing TAPBPR has preference for HLA-A, particularly for supertypes A2 and A24, over HLA-B and -C molecules. Keywords: MHC, HLA, polymorphism, TAPBPR/TAPBPL, antigen processing and presentationhttp://www.sciencedirect.com/science/article/pii/S2211124719312719 |
| spellingShingle | F. Tudor Ilca Linnea Z. Drexhage Gemma Brewin Sarah Peacock Louise H. Boyle Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR Cell Reports |
| title | Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR |
| title_full | Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR |
| title_fullStr | Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR |
| title_full_unstemmed | Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR |
| title_short | Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR |
| title_sort | distinct polymorphisms in hla class i molecules govern their susceptibility to peptide editing by tapbpr |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719312719 |
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