HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4-positive T lymphocytes from patients with cystic fibrosis.
Clin Exp Allergy
; 45(8): 1305-16, 2015 Aug.
Article
en En
| MEDLINE
| ID: mdl-25851465
ABSTRACT
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*0501 (patient 1) and HLA-DQB1*0201 (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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sulfametoxazol
/
Activación de Linfocitos
/
Linfocitos T CD4-Positivos
/
Fibrosis Quística
/
Proliferación Celular
/
Hipersensibilidad a las Drogas
/
Alelos
/
Cadenas beta de HLA-DQ
Límite:
Female
/
Humans
/
Male
Idioma:
En
Año:
2015
Tipo del documento:
Article