Avidity determines T-cell reactivity in abacavir hypersensitivity.

Détails

ID Serval
serval:BIB_AD82250129BE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Avidity determines T-cell reactivity in abacavir hypersensitivity.
Périodique
European Journal of Immunology
Auteur⸱e⸱s
Adam J., Eriksson K.K., Schnyder B., Fontana S., Pichler W.J., Yerly D.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
42
Numéro
7
Pages
1706-1716
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity reactions in HLA-B*5701(+) individuals. To understand the abc-specific activation of CD8(+) T cells, we generated abc-specific T-cell clones (abc-TCCs). Abc reactivity could not be linked to the metabolism and/or processing of the drug, since abc metabolizing enzymes were not expressed in immune cells and inhibition of the proteasome in APCs did not affect TCC reactivity. Ca(2+) influx assays revealed different reactivity patterns of abc-TCCs. While all TCCs reacted to abc presented on HLA-B*5701 molecules, a minority also reacted immediately to abc in solution. Titration experiments showed that the ability to react immediately to abc correlated significantly with the TCR avidity of the T cells. Modifications of soluble abc concentrations revealed that the reactivity patterns of abc-TCCs were not fixed but dynamic. When TCCs with an intermediate TCR avidity were stimulated with increasing abc concentrations, they showed an accelerated activation kinetic. Thus, they reacted immediately to the drug, similar to the reaction of TCCs of high avidity. The observed immediate activation and the noninvolvement of the proteasome suggest that, in contrast to haptens, abc-specific T-cell stimulation does not require the formation of covalent bonds to produce a neo-antigenic determinant.
Mots-clé
Anti-HIV Agents/adverse effects, Anti-HIV Agents/immunology, Antibody Affinity, CD8-Positive T-Lymphocytes/immunology, Calcium/analysis, Calcium/immunology, Clone Cells, Dideoxynucleosides/adverse effects, Dideoxynucleosides/immunology, Dose-Response Relationship, Drug, Drug Hypersensitivity/etiology, Drug Hypersensitivity/immunology, HLA-B Antigens/immunology, Humans, Kinetics, Leukocytes, Mononuclear/drug effects, Leukocytes, Mononuclear/immunology, Lymphocyte Activation, Proteome/immunology, Statistics, Nonparametric
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/11/2014 17:28
Dernière modification de la notice
20/08/2019 15:17
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