Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity

被引：273

作者：

Chessman, Diana ^{[2
]}

Kostenko, Lyudmila ^{[2
]}

Lethborg, Tessa ^{[2
]}

Purcell, Anthony W. ^{[3
]}

Williamson, Nicholas A. ^{[3
]}

Chen, Zhenjun ^{[2
]}

Kjer-Nielsen, Lars ^{[2
]}

Mifsud, Nicole A. ^{[2
]}

Tait, Brian D. ^{[4
]}

Holdsworth, Rhonda ^{[4
]}

Almeida, Coral Ann ^{[5
]}

Nolan, David ^{[5
]}

Macdonalds, Whitney A. ^{[1
]}

Archbold, Julia K. ^{[1
]}

Kellerher, Anthony D. ^{[6
]}

Marriott, Debbie ^{[7
]}

Mallal, Simon

Bharadwaj, Mandvi ^{[2
]}

Rossjohn, Jamie ^{[1
]}

McCluskey, James ^{[2
]}

机构：

[1] Monash Univ, Prot Crystallog Unit, Dept Biochem & Mol Biol, Sch Biomed Sci, Clayton, Vic 3800, Australia

[2] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia

[3] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia

[4] Australian Red Cross Blood Serv, Victorian Transplantat & Immunogenet Serv, S Melbourne, Vic 3205, Australia

[5] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia

[6] St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia

[7] Natl Ctr HIV Epidemiol & Clin Res UNSW, Sydney, NSW, Australia

来源：

IMMUNITY | 2008年 / 28卷 / 06期

基金：

澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

D O I：

10.1016/j.immuni.2008.04.020

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

The basis for strong immunogenetic associations between particular human leukocyte antigen (HLA) class I allotypes and inflammatory conditions like Behcet'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 (HI-A-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.

引用

页码：822 / 832

页数：11

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