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http://purl.uniprot.org/citations/35963284http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35963284http://www.w3.org/2000/01/rdf-schema#comment"Flucloxacillin (FLX) induces adverse liver reactions, which has been reported to be related to human leukocyte antigen (HLA)-B*57:01. In a previous study, abacavir-induced hypersensitivity was induced in HLA-B*57:01-transgenic mice (B*57:01-Tg), originally constructed by our group (Susukida et al., 2021). In this study, B*57:01-Tg mice were used to reproduce FLX-induced liver injury. However, treatment of B*57:01-Tg mice with FLX alone did not increase serum ALT levels. Immune-deficient B*57:01-Tg/PD-1-/-mice were produced by mating B*57:01-Tg with PD-1-/- mice. The immune response of B*57:01-Tg/PD-1-/- mice was further modulated by co-administration of CpG-oligodeoxynucleotides and anti-CD4 mAb. Nevertheless, immune regulation in B*57:01-Tg mice did not contribute to the onset of FLX-induced liver injury or immune activation. Moreover, we generated an FLX-human serum albumin (HSA) conjugate and showed that FLX covalently bound to HSA in a time-dependent manner. The FLX-HSA conjugate was administered to the B*57:01-Tg mice. The immune response was investigated using flow cytometry, revealing the phenotype of CD44highCD62Llow in CD8+ T cells (TEM cells). Administration of the FLX-HSA conjugate resulted in an HLA-B*57:01 restricted immune response as shown by the stimulation of TEM cells in the draining lymph nodes. In conclusion, administration of FLX alone to B*57:01-Tg mice did not induce liver injury or immune activation. Immune system sensitivity does not play a decisive role in this process. The conjugation of FLX and HSA results in specific TEM cell stimulation, which suggests that HLA-B*57:01 drives a stronger interaction with CD8+ T cells. These results suggest that patients carrying HLA-B*57:01 could be more susceptible to a conjugate of FLX and albumin and drive CD8+ T cell activation, which may be a vital risk factor for FLX-induced liver injury. In addition, the application of the FLX-HSA adduct may be an effective method for the construction of FLX-induced idiosyncratic liver injury in mice."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.org/dc/terms/identifier"doi:10.1016/j.imlet.2022.08.002"xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/author"Aoki S."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/author"Gao Y."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/author"Ito K."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/author"Song B."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/name"Immunol Lett"xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/pages"5-11"xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/title"Conjugation of human serum albumin and flucloxacillin provokes specific immune response in HLA-B*57:01 transgenic mice."xsd:string
http://purl.uniprot.org/citations/35963284http://purl.uniprot.org/core/volume"249"xsd:string
http://purl.uniprot.org/citations/35963284http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35963284
http://purl.uniprot.org/citations/35963284http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35963284
http://purl.uniprot.org/uniprot/#_Q02242-mappedCitation-35963284http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35963284
http://purl.uniprot.org/uniprot/#_Q544F3-mappedCitation-35963284http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35963284
http://purl.uniprot.org/uniprot/Q02242http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35963284
http://purl.uniprot.org/uniprot/Q544F3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35963284