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- Title
Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire.
- Authors
Illing, Patricia T.; van Hateren, Andy; Darley, Rachel; Croft, Nathan P.; Mifsud, Nicole A.; King, Samuel; Kostenko, Lyudmila; Bharadwaj, Mandvi; McCluskey, James; Elliott, Tim; Purcell, Anthony W.
- Abstract
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.
- Subjects
MAJOR histocompatibility complex; T cell receptors; ANTIGENS; ABACAVIR; T cells; DRUG allergy
- Publication
Frontiers in Immunology, 2021, Vol 12, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2021.672737