PMID- 23046128
OWN - NLM
STAT- MEDLINE
DCOM- 20130225
LR  - 20121010
IS  - 1600-065X (Electronic)
IS  - 0105-2896 (Linking)
VI  - 250
IP  - 1
DP  - 2012 Nov
TI  - The structural basis of HLA-associated drug hypersensitivity syndromes.
PG  - 158-66
LID - 10.1111/j.1600-065X.2012.01163.x [doi]
AB  - 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.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Pompeu, Yuri A
AU  - Pompeu YA
AD  - Department of Chemistry, University of Florida, Gainesville, USA.
FAU - Stewart, Jon D
AU  - Stewart JD
FAU - Mallal, Simon
AU  - Mallal S
FAU - Phillips, Elizabeth
AU  - Phillips E
FAU - Peters, Bjoern
AU  - Peters B
FAU - Ostrov, David A
AU  - Ostrov DA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Immunol Rev
JT  - Immunological reviews
JID - 7702118
RN  - 0 (Autoantigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Xenobiotics)
SB  - IM
MH  - Antigen-Presenting Cells/cytology/immunology/metabolism
MH  - Autoantigens/*chemistry/immunology/metabolism
MH  - Binding Sites
MH  - Drug Hypersensitivity/etiology/*immunology
MH  - HLA Antigens/*chemistry/immunology/metabolism
MH  - Humans
MH  - Ligands
MH  - Models, Molecular
MH  - Peptides/*chemistry/immunology/metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Receptors, Antigen, T-Cell/*chemistry/immunology/metabolism
MH  - Syndrome
MH  - T-Lymphocytes/cytology/immunology/metabolism
MH  - Xenobiotics/adverse effects/*chemistry
EDAT- 2012/10/11 06:00
MHDA- 2013/02/26 06:00
CRDT- 2012/10/11 06:00
PHST- 2012/10/11 06:00 [entrez]
PHST- 2012/10/11 06:00 [pubmed]
PHST- 2013/02/26 06:00 [medline]
AID - 10.1111/j.1600-065X.2012.01163.x [doi]
PST - ppublish
SO  - Immunol Rev. 2012 Nov;250(1):158-66. doi: 10.1111/j.1600-065X.2012.01163.x.