Journal article
Human leukocyte Antigen Class I-restricted activation of CD8+ T Cells provides the immunogenetic basis of a systemic drug hypersensitivity
Immunity, Vol.28(6), pp.822-832
2008
Abstract
The basis for strong immunogenetic associations between particular human leukocyte antigen (HLA) class I allotypes and inflammatory conditions like Behçet's disease (HLA-B51) and ankylosing spondylitis (HLA-B27) remain mysterious. Recently, however, even stronger HLA associations are reported in drug hypersensitivities to the reverse-transcriptase inhibitor abacavir (HLA-B57), the gout prophylactic allopurinol (HLA-B58), and the antiepileptic carbamazepine (HLA-B∗1502), providing a defined disease trigger and suggesting a general mechanism for these associations. We show that systemic reactions to abacavir were driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells. Recognition of abacavir required the transporter associated with antigen presentation and tapasin, was fixation sensitive, and was uniquely restricted by HLA-B∗5701 and not closely related HLA allotypes with polymorphisms in the antigen-binding cleft. Hence, the strong association of HLA-B∗5701 with abacavir hypersensitivity reflects specificity through creation of a unique ligand as well as HLA-restricted antigen presentation, suggesting a basis for the strong HLA class I-association with certain inflammatory disorders.
Details
- Title
- Human leukocyte Antigen Class I-restricted activation of CD8+ T Cells provides the immunogenetic basis of a systemic drug hypersensitivity
- Authors/Creators
- D. Chessman (Author/Creator) - The University of MelbourneL. Kostenko (Author/Creator) - The University of MelbourneT. Lethborg (Author/Creator) - The University of MelbourneA.W. Purcell (Author/Creator) - The University of MelbourneN.A. Williamson (Author/Creator) - The University of MelbourneZ. Chen (Author/Creator) - The University of MelbourneL. Kjer-Nielsen (Author/Creator) - The University of MelbourneN.A. Mifsud (Author/Creator) - The University of MelbourneB.D. Tait (Author/Creator) - Australian Red Cross LifebloodR. Holdsworth (Author/Creator) - Australian Red Cross LifebloodC.M. Almeida (Author/Creator)D. Nolan (Author/Creator) - Royal Perth HospitalW.A. Macdonald (Author/Creator) - Monash UniversityJ.K. Archbold (Author/Creator) - Monash UniversityA.D. Kellerher (Author/Creator) - National Centre for Immunisation Research & SurveillanceD. Marriott (Author/Creator) - St Vincent's HealthS. Mallal (Author/Creator) - Royal Perth HospitalM. Bharadwaj (Author/Creator) - The University of MelbourneJ. Rossjohn (Author/Creator) - Monash UniversityJ. McCluskey (Author/Creator) - The University of Melbourne
- Publication Details
- Immunity, Vol.28(6), pp.822-832
- Publisher
- Cell Press/Elsevier
- Identifiers
- 991005541638307891
- Copyright
- © 2008 Elsevier Inc.
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology