Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire.
Front Immunol
; 12: 672737, 2021.
Article
em En
| MEDLINE
| ID: mdl-34093574
ABSTRACT
Abacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*5701 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*5701 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*5701 peptide complexes. We show that whilst abacavir had minimal impact on the maturation or average stability of HLA-B*5701 molecules, abacavir was able to differentially enhance the formation, selectively decrease the dissociation, and alter tapasin loading dependency of certain HLA-B*5701-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Didesoxinucleosídeos
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Antígenos HLA-B
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Fármacos Anti-HIV
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Hipersensibilidade a Drogas
Limite:
Humans
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Austrália