Active suppression rather than ignorance: tolerance to abacavir-induced HLA-B*57:01 peptide repertoire alteration

The Journal of Clinical Investigation
Elizabeth Phillips, Simon Mallal

Abstract

The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation. This report potentially explains why 45% of HLA-B*57:01 carriers tolerate abacavir and provides a framework for future studies of HLA-restricted, T cell-mediated drug tolerance and hypersensitivity.

References

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Citations

Jul 26, 2018·Allergy·Maria J Torres, Tahia D Fernández
May 1, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Cristina OlteanuRoni P Dodiuk-Gad
Mar 16, 2021·Frontiers in Immunology·Yun-Shiuan Olivia HsuChun-Bing Chen
May 28, 2021·Current Opinion in Allergy and Clinical Immunology·Rebecca J HertzmanElizabeth J Phillips

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Methods Mentioned

BETA
biopsies

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