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http://purl.uniprot.org/citations/25851465http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25851465http://www.w3.org/2000/01/rdf-schema#comment"

Background

For certain HLA allele-associated drug hypersensitivity reactions, the parent drug has been shown to associate directly with the risk allele. In other forms of hypersensitivity, HLA risk alleles have not been identified and T cells are activated in an allele unrestricted manner. Chemically reactive drug metabolites bind to multiple proteins; thus, it is assumed that the derived peptide antigens interact with a number of HLA molecules to activate T cells; however, HLA restriction of the drug metabolite-specific T-cell response has not been studied.

Objective

To utilize T cells from sulfamethoxazole (SMX) hypersensitive patients with cystic fibrosis to examine the HLA molecules that interact with nitroso SMX (SMX-NO)-derived antigens.

Methods

T-cell clones were generated from 4 hypersensitive patients. Drug-specific proliferative responses and cytokine secretion were measured. Anti-human class I and class II antibodies were used to analyse HLA restriction. Antigen-presenting cells expressing different HLA molecules were used to determine the alleles involved in the presentation of SMX-NO-derived antigens to T cells.

Results

A total of 976 clones were tested for SMX-NO reactivity. Thirty-nine CD4+ clones were activated with SMX-NO and found to proliferate and secrete cytokines. The SMX-NO-specific response was blocked with an antibody against HLA-DQ. SMX-NO-specific responses were detected with antigen-presenting cells expressing HLA-DQB1*05:01 (patient 1) and HLA-DQB1*02:01 (patient 2), but not other HLA-DQB1 alleles.

Conclusion and clinical relevance

HLA-DQ plays an important role in the activation of SMX-NO-specific CD4+ T cells. Detection of HLA-DQ allele-restricted responses suggests that T cells are activated by a limited repertoire of SMX-NO-modified peptides."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.org/dc/terms/identifier"doi:10.1111/cea.12546"xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Faulkner L."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Sette A."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Baker D.M."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Pirmohamed M."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Park B.K."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Alfirevic A."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Whitaker P."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Naisbitt D.J."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Peckham D."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Ogese M.O."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/author"Saide K."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/name"Clin Exp Allergy"xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/pages"1305-1316"xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/title"HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4-positive T lymphocytes from patients with cystic fibrosis."xsd:string
http://purl.uniprot.org/citations/25851465http://purl.uniprot.org/core/volume"45"xsd:string
http://purl.uniprot.org/citations/25851465http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25851465
http://purl.uniprot.org/citations/25851465http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25851465
http://purl.uniprot.org/uniprot/#_A0A0E3DC97-mappedCitation-25851465http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25851465
http://purl.uniprot.org/uniprot/#_A0A0E3DC99-mappedCitation-25851465http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25851465
http://purl.uniprot.org/uniprot/#_A0A076L4M5-mappedCitation-25851465http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25851465
http://purl.uniprot.org/uniprot/#_A0A0A7C7I5-mappedCitation-25851465http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25851465
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