Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire
Abacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*57:01 major histocompatibility complex class I allotype when utilising the drug abacavir as a part of their anti-retroviral regimen. The drug is known to bind within the HLA-B*57:01 antigen binding cleft, leading to the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.672737/full |
| _version_ | 1818865596508405760 |
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| author | Patricia T. Illing Andy van Hateren Rachel Darley Nathan P. Croft Nicole A. Mifsud Samuel King Lyudmila Kostenko Mandvi Bharadwaj James McCluskey Tim Elliott Tim Elliott Anthony W. Purcell |
| author_facet | Patricia T. Illing Andy van Hateren Rachel Darley Nathan P. Croft Nicole A. Mifsud Samuel King Lyudmila Kostenko Mandvi Bharadwaj James McCluskey Tim Elliott Tim Elliott Anthony W. Purcell |
| author_sort | Patricia T. Illing |
| collection | DOAJ |
| description | Abacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*57:01 major histocompatibility complex class I allotype when utilising the drug abacavir as a part of their anti-retroviral regimen. The drug is known to bind within the HLA-B*57:01 antigen binding cleft, leading to the selection of novel self-peptide ligands, thus provoking life-threatening immune responses. However, the sub-cellular location of abacavir binding and the mechanics of altered peptide selection are not well understood. Here, we probed the impact of abacavir on the assembly of HLA-B*57:01 peptide complexes. We show that whilst abacavir had minimal impact on the maturation or average stability of HLA-B*57:01 molecules, abacavir was able to differentially enhance the formation, selectively decrease the dissociation, and alter tapasin loading dependency of certain HLA-B*57:01-peptide complexes. Our data reveals a spectrum of abacavir mediated effects on the immunopeptidome which reconciles the heterogeneous functional T cell data reported in the literature. |
| first_indexed | 2024-12-19T10:50:04Z |
| format | Article |
| id | doaj.art-aa6e9a64a82f4a819e31c997dcdb4c3e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T10:50:04Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa6e9a64a82f4a819e31c997dcdb4c3e2022-12-21T20:25:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.672737672737Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide RepertoirePatricia T. Illing0Andy van Hateren1Rachel Darley2Nathan P. Croft3Nicole A. Mifsud4Samuel King5Lyudmila Kostenko6Mandvi Bharadwaj7James McCluskey8Tim Elliott9Tim Elliott10Anthony W. Purcell11Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaInstitute for Life Sciences and Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United KingdomInstitute for Life Sciences and Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United KingdomInfection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaInfection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaInstitute for Life Sciences and Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United KingdomDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaInstitute for Life Sciences and Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomInfection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaAbacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*57:01 major histocompatibility complex class I allotype when utilising the drug abacavir as a part of their anti-retroviral regimen. The drug is known to bind within the HLA-B*57:01 antigen binding cleft, leading to the selection of novel self-peptide ligands, thus provoking life-threatening immune responses. However, the sub-cellular location of abacavir binding and the mechanics of altered peptide selection are not well understood. Here, we probed the impact of abacavir on the assembly of HLA-B*57:01 peptide complexes. We show that whilst abacavir had minimal impact on the maturation or average stability of HLA-B*57:01 molecules, abacavir was able to differentially enhance the formation, selectively decrease the dissociation, and alter tapasin loading dependency of certain HLA-B*57:01-peptide complexes. Our data reveals a spectrum of abacavir mediated effects on the immunopeptidome which reconciles the heterogeneous functional T cell data reported in the literature.https://www.frontiersin.org/articles/10.3389/fimmu.2021.672737/fullMHC I antigen presentationabacavirT cellsdrug hypersensitivityimmunopeptidometapasin |
| spellingShingle | Patricia T. Illing Andy van Hateren Rachel Darley Nathan P. Croft Nicole A. Mifsud Samuel King Lyudmila Kostenko Mandvi Bharadwaj James McCluskey Tim Elliott Tim Elliott Anthony W. Purcell Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire Frontiers in Immunology MHC I antigen presentation abacavir T cells drug hypersensitivity immunopeptidome tapasin |
| title | Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire |
| title_full | Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire |
| title_fullStr | Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire |
| title_full_unstemmed | Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire |
| title_short | Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire |
| title_sort | kinetics of abacavir induced remodelling of the major histocompatibility complex class i peptide repertoire |
| topic | MHC I antigen presentation abacavir T cells drug hypersensitivity immunopeptidome tapasin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.672737/full |
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