Document Detail

The structural basis of HLA-associated drug hypersensitivity syndromes.
MedLine Citation:
PMID:  23046128     Owner:  NLM     Status:  In-Data-Review    
Recent data suggest alternative mechanisms that promote human leukocyte antigen (HLA)-associated drug syndromes. Hypersensitive responses have been attributed to drug interactions with HLA molecules, peptides presented by HLA molecules and T-cell antigen receptors. Definition of an increasing number of HLA-associated drug syndromes suggests that polymorphism in the antigen-binding cleft residues influence recognition of specific drugs. Recent data demonstrate that small molecule drugs bind within the antigen-binding cleft of HLA in a manner that alters the repertoire of HLA-bound peptide ligands. This drug recognition mechanism permits presentation of self-peptides to which the host has not been tolerized. This altered repertoire mechanism is analogous to massive polyclonal T-cell responses occurring in mismatched HLA organ transplantation in which the drug in effect creates a novel HLA allele. Alteration of the self-peptide repertoire by HLA-binding small molecules may be the mechanistic basis for a diverse set of deleterious T-cell responses since the antigen-binding cleft has structural features that are compatible with binding drug-like small molecules. Small molecule drugs that bind elements of the trimolecular complex (T-cell receptor, peptide, and HLA) may cause short- and long-term adverse effects by a diverse set of mechanisms.
Yuri A Pompeu; Jon D Stewart; Simon Mallal; Elizabeth Phillips; Bjoern Peters; David A Ostrov
Related Documents :
23599788 - Androgen receptor decreases the cytotoxic effects of chemotherapeutic drugs in upper ur...
23789948 - Transporters at cns barrier sites: obstacles or opportunities for drug delivery?
24094158 - Co-delivery of drug and dna from cationic dual-responsive micelles derived from poly(dm...
24091428 - Poly(acrylic acid)-block-poly(vinyl alcohol) anchored maghemite nanoparticles designed ...
6658828 - The transplacental effects of ethanol and metronidazole in swiss webster mice.
7475508 - Electrophoretic evaluation of the mobility of drugs suitable for iontophoresis.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Immunological reviews     Volume:  250     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  158-66     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Department of Chemistry, University of Florida, Gainesville, FL, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Conformational variation in structures of classical and non-classical MHCII proteins and functional ...
Next Document:  Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells.