PMID- 18549801
OWN - NLM
STAT- MEDLINE
DCOM- 20080710
LR  - 20130524
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Linking)
VI  - 28
IP  - 6
DP  - 2008 Jun
TI  - Human leukocyte antigen class I-restricted activation of CD8+ T cells provides 
      the immunogenetic basis of a systemic drug hypersensitivity.
PG  - 822-32
LID - 10.1016/j.immuni.2008.04.020 [doi]
AB  - 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 (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.
FAU - Chessman, Diana
AU  - Chessman D
AD  - Department of Microbiology & Immunology, The University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Kostenko, Lyudmila
AU  - Kostenko L
FAU - Lethborg, Tessa
AU  - Lethborg T
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - Williamson, Nicholas A
AU  - Williamson NA
FAU - Chen, Zhenjun
AU  - Chen Z
FAU - Kjer-Nielsen, Lars
AU  - Kjer-Nielsen L
FAU - Mifsud, Nicole A
AU  - Mifsud NA
FAU - Tait, Brian D
AU  - Tait BD
FAU - Holdsworth, Rhonda
AU  - Holdsworth R
FAU - Almeida, Coral Ann
AU  - Almeida CA
FAU - Nolan, David
AU  - Nolan D
FAU - Macdonald, Whitney A
AU  - Macdonald WA
FAU - Archbold, Julia K
AU  - Archbold JK
FAU - Kellerher, Anthony D
AU  - Kellerher AD
FAU - Marriott, Debbie
AU  - Marriott D
FAU - Mallal, Simon
AU  - Mallal S
FAU - Bharadwaj, Mandvi
AU  - Bharadwaj M
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - McCluskey, James
AU  - McCluskey J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - 0 (HLA-B*57:03 antigen)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - WR2TIP26VS (abacavir)
SB  - IM
EIN - Immunity. 2008 Jul;29(1):165
MH  - Anti-HIV Agents/adverse effects/immunology/metabolism
MH  - Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dideoxynucleosides/*adverse effects/immunology/metabolism
MH  - Drug Hypersensitivity/*immunology/metabolism
MH  - HLA-B Antigens/chemistry/*immunology/metabolism
MH  - Humans
MH  - *Lymphocyte Activation
MH  - Reverse Transcriptase Inhibitors/*adverse effects/immunology/metabolism
EDAT- 2008/06/14 09:00
MHDA- 2008/07/11 09:00
CRDT- 2008/06/14 09:00
PHST- 2007/12/28 00:00 [received]
PHST- 2008/03/25 00:00 [revised]
PHST- 2008/04/01 00:00 [accepted]
PHST- 2008/06/14 09:00 [pubmed]
PHST- 2008/07/11 09:00 [medline]
PHST- 2008/06/14 09:00 [entrez]
AID - S1074-7613(08)00242-2 [pii]
AID - 10.1016/j.immuni.2008.04.020 [doi]
PST - ppublish
SO  - Immunity. 2008 Jun;28(6):822-32. doi: 10.1016/j.immuni.2008.04.020.