Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire.
Front Immunol
; 12: 672737, 2021.
Article
in 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Dideoxynucleosides
/
HLA-B Antigens
/
Anti-HIV Agents
/
Drug Hypersensitivity
Limits:
Humans
Language:
En
Journal:
Front Immunol
Year:
2021
Type:
Article
Affiliation country:
Australia