Epitopes described in "Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene."

Article Authors:Chris Pickard; Andrew M Smith; Hywel Cooper; Ian Strickland; John Jackson; Eugene Healy; Peter S Friedmann
Article Title:Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene.
Reference Detail
Reference ID:1007790
Abstract:T-cell mediated contact sensitization by small molecular weight xenobiotics results in significant morbidity and absences from work. To be recognized by T-cells, xenobiotics must act as haptens, becoming protein-bound. At present, the requirement for processing and presentation of xenobiotics, the nature of the T-cell responses to them and the mechanisms that confer individual susceptibility in humans are unclear. We have investigated the T-cell response to the hapten 2,4-dinitrochlorobenzene (DNCB) which can sensitize all immunocompetent people. Fourteen healthy adults were sensitized with DNCB; 11 demonstrated positive T-cell responses to the chemical in vitro. Responding cells were of both CD4+ and CD8+ subsets, of Th1 and Tc1 phenotypes, producing high levels of IFN-gamma and low levels of IL-10. DNCB-specific T-cell clones were raised from 2 subjects, which in the presence of fixed and unfixed autologous Epstein-Barr virus transformed B cells as antigen-presenting-cells (APC), demonstrated that the chemical requires metabolic processing by the APC in order to initiate the T-cell response. Intracellular-reduced glutathione is consumed in detoxication of DNCB, leaving residual non-detoxified DNCB free to bind to proteins. The results suggest that DNCB forms multiple haptens with intracellular and extracellular proteins leading to Th1 and Tc1 responses in individuals exposed to this compound.
Reference Type:Literature
PubMed ID:17008874
Journal:J Invest Dermatol
Journal Volume:127
Article Pages:630-7
Journal ISSN:1523-1747
Article Chemical List:Haptens;Xenobiotics;Interleukin-10;Interferon-gamma;Dinitrochlorobenzene
Article MeSH List:Adult; Antigen-Presenting Cells(metabolism); Cell Line, Transformed; Cell Proliferation(drug effects); Dinitrochlorobenzene(pharmacology); Female; Haptens(chemistry); Herpesvirus 4, Human(metabolism); Humans; Interferon-gamma(metabolism); Interleukin-10(biosynthesis); Lymphocyte Activation(drug effects); Male; T-Lymphocytes(drug effects); Xenobiotics(chemistry)
Curation Last Updated:2016-05-11 20:03:37