Identification of Flucloxacillin-Haptenated HLA-B*57:01 Ligands: Evidence of Antigen Processing and Presentation.
Toxicol Sci
; 177(2): 454-465, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-32726429
ABSTRACT
Flucloxacillin is a ß-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of human leukocyte antigen (HLA)-B*5701 increases susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the modification of peptides that are presented by the risk allele. In this study, the binding of flucloxacillin to immune cells was characterized and the nature of the peptides presented by HLA-B*5701 was analyzed using mass spectrometric-based immunopeptidomics methods. Flucloxacillin modification of multiple proteins was observed, providing a potential source of neoantigens for HLA presentation. Of the peptides eluted from flucloxacillin-treated C1R-B*5701 cells, 6 putative peptides were annotated as flucloxacillin-modified HLA-B*5701 peptide ligands (data are available via ProteomeXchange with identifier PXD020137). To conclude, we have characterized naturally processed drug-haptenated HLA ligands presented on the surface of antigen presenting cells that may drive drug-specific CD8+ T-cell responses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apresentação de Antígeno
/
Floxacilina
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Toxicol Sci
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido