Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR
| Autor: | Ilca, F Tudor, Drexhage, Linnea Z, Brewin, Gemma, Peacock, Sarah, Boyle, Louise H |
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Antigen Presentation
Polymorphism Genetic HLA-A Antigens Histocompatibility Antigens Class I HLA-A24 Antigen Immunoglobulins Membrane Proteins Membrane Transport Proteins HLA-C Antigens 3. Good health polymorphism HLA HEK293 Cells Protein Domains HLA-B Antigens HLA-A2 Antigen TAPBPR/TAPBPL Humans antigen processing and presentation MHC Immunoglobulin Allotypes Peptides HeLa Cells Molecular Chaperones Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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