Journal article

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

FRONTIERS IN IMMUNOLOGY | FRONTIERS MEDIA SA | Published : 2021

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 HL..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council Australia (NHMRC)


Awarded by Cancer Research UK programme


Awarded by BBSRC


Awarded by NHMRC Early Career Fellowship


Awarded by NHMRC Principal Research Fellowship


Funding Acknowledgements

This work was funded by the National Health and Medical Research Council Australia (NHMRC) Project grants 1122099 and 1165490 (awarded to AP) and by a Cancer Research UK programme grant C7056A and BBSRC project grant BB/L010402/1 (both awarded to TE). PI was supported by a NHMRC Early Career Fellowship (1072159) and a Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship. AP acknowledges salary support from a NHMRC Principal Research Fellowship (1137739).