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

Phillips EJ, Mallal SA
J Clin Invest. 2018 128 (7): 2746-2749

PMID: 29781810 · PMCID: PMC6025972 · DOI:10.1172/JCI121525

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.

MeSH Terms (8)

Animals Dideoxynucleosides Drug Hypersensitivity Drug Tolerance HLA-B Antigens Mice Mice, Transgenic Peptides

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