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

Frontiers in Immunology

Mandvi Bharadwaj¹  James McCluskey¹  Lyudmila Kostenko¹  Patricia T. Illing²  Anthony W. Purcell²  Nicole A. Mifsud²  Nathan P. Croft²  Samuel King³  Rachel Darley³  Andy van Hateren³  Tim Elliott⁴ 

[1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia;Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia;Institute for Life Sciences and Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;

关键词: MHC I antigen presentation;    abacavir;    T cells;    drug hypersensitivity;    immunopeptidome;    tapasin;   

DOI  :  10.3389/fimmu.2021.672737

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown