title: HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.
abstract: BACKGROUND
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can involve MHC-restricted presentation of a drug or its metabolites for T-cell activation. HLA-B(*)1502 tightly associated with carbamazepine (CBZ) induced these conditions in a Han Chinese population.
  
  
  OBJECTIVE
  We sought to identify HLA-B(*)1502-bound peptides that might be involved in CBZ-induced SJS/TEN.
  
  
  METHODS
  Soluble HLA-B(*)1502 was used to identify bound peptides in the presence and absence of CBZ by using liquid chromatography-tandem mass spectrometry. Peptide-binding assays were performed to detect the specific interaction between the HLA molecule and the identified peptides. Mass spectra were compared to detect CBZ-modified peptides.
  
  
  RESULTS
  We identified more than 145 peptides bound to HLA-B(*)1502. In 13 of 15 peptides examined, we functionally confirmed their specificity with binding assays. Preferable uses of these peptides at the anchoring residues P2 and P9 were similar to those observed in other HLA-B alleles in the Han Chinese population. However, the preferable use of serine residues at the nonanchoring position (P) 5, P6, P7, and P8 appeared to be unique for the B(*)1502 peptides. No specific CBZ-modified peptides were detected when we compared the mass spectra of peptides detected in the presence or absence of the drug.
  
  
  CONCLUSIONS
  Noncovalent interaction between a drug and an HLA complex might contribute to cytotoxic T cell-mediated cell death in patients with SJS/TEN.
  
  
  CONCLUSIONS
  An understanding of pharmacologic interaction of drugs with an HLA complex might lead to safer drugs that avoid SJS/TEN.
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Chih-Wen Ou
authors: CW
authors: Yang
authors: Shuen-Iu
authors: SI
authors: Hung
authors: Chiun-Gung
authors: CG
authors: Juo
authors: Ya-Ping
authors: YP
authors: Lin
authors: Wu-Hsiang
authors: WH
authors: Fang
authors: I-Hsuan
authors: IH
authors: Lu
authors: Shui-Tein
authors: ST
authors: Chen
authors: Yuan-Tsong
authors: YT
authors: Chen
mesh_terms: D002220:Carbamazepine / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis / Q000378:metabolism*; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced*
chemical_list: D015235:HLA-B Antigens; D010455:Peptides; D002220:Carbamazepine