| http://purl.uniprot.org/citations/33633747 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33633747 | http://www.w3.org/2000/01/rdf-schema#comment | "Neoantigen formation due to the interaction of drug molecules with human leukocyte antigen (HLA)-peptide complexes can lead to severe hypersensitivity reactions. Flucloxacillin (FLX), a β-lactam antibiotic for narrow-spectrum gram-positive bacterial infections, has been associated with severe immune-mediated drug-induced liver injury caused by an influx of T-lymphocytes targeting liver cells potentially recognizing drug-haptenated peptides in the context of HLA-B*57:01. To identify immunopeptidome changes that could lead to drug-driven immunogenicity, we used mass spectrometry to characterize the proteome and immunopeptidome of B-lymphoblastoid cells solely expressing HLA-B*57:01 as MHC-I molecules. Selected drug-conjugated peptides identified in these cells were synthesized and tested for their immunogenicity in HLA-B*57:01-transgenic mice. T cell responses were evaluated in vitro by immune assays. The immunopeptidome of FLX-treated cells was more diverse than that of untreated cells, enriched with peptides containing carboxy-terminal tryptophan and FLX-haptenated lysine residues on peptides. Selected FLX-modified peptides with drug on P4 and P6 induced drug-specific CD8+ T cells in vivo. FLX was also found directly linked to the HLA K146 that could interfere with KIR-3DL or peptide interactions. These studies identify a novel effect of antibiotics to alter anchor residue frequencies in HLA-presented peptides which may impact drug-induced inflammation. Covalent FLX-modified lysines on peptides mapped drug-specific immunogenicity primarily at P4 and P6 suggesting these peptide sites as drivers of off-target adverse reactions mediated by FLX. FLX modifications on HLA-B*57:01-exposed lysines may also impact interactions with KIR or TCR and subsequent NK and T cell function."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.org/dc/terms/identifier | "doi:10.3389/fimmu.2020.629399"xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Takahashi M."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Natarajan K."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Walker L.M."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Su S."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Norcross M.A."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Roderiquez G."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Margulies D.H."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Puig M."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Boyd L.F."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Hildebrand W.H."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Venna R."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Cardone M."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Wu W.W."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Mattson E."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Ananthula S."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Abdoulaeva G."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Beaucage S.L."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/author | "Kumar Polumuri S."xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/name | "Front Immunol"xsd:string |
| http://purl.uniprot.org/citations/33633747 | http://purl.uniprot.org/core/pages | "629399"xsd:string |