Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire

Patricia T. Illing, Andy van Hateren, Rachel Darley, Nathan P. Croft, Nicole A. Mifsud, Samuel King, Lyudmila Kostenko, Mandvi Bharadwaj, James McCluskey, Tim Elliott, Anthony W. Purcell

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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.

Original languageEnglish
Article number672737
Number of pages19
JournalFrontiers in Immunology
Publication statusPublished - 19 May 2021


  • abacavir
  • drug hypersensitivity
  • immunopeptidome
  • MHC I antigen presentation
  • peptide selection
  • T cells
  • tapasin

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