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Stimulation of human T cells with sulfonamides and sulfonamide metabolites  J. Luis Castrejon, BSc, Neil Berry, PhD, Sabah El-Ghaiesh, BSc, Basil Gerber,

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Presentation on theme: "Stimulation of human T cells with sulfonamides and sulfonamide metabolites  J. Luis Castrejon, BSc, Neil Berry, PhD, Sabah El-Ghaiesh, BSc, Basil Gerber,"— Presentation transcript:

1 Stimulation of human T cells with sulfonamides and sulfonamide metabolites 
J. Luis Castrejon, BSc, Neil Berry, PhD, Sabah El-Ghaiesh, BSc, Basil Gerber, PhD, Werner J. Pichler, MD, B. Kevin Park, PhD, Dean J. Naisbitt, PhD  Journal of Allergy and Clinical Immunology  Volume 125, Issue 2, Pages e4 (February 2010) DOI: /j.jaci Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Stimulation of individual SMX-specific, SMX metabolite–specific, and cross-reactive T-cell clones from 3 patients (1, 2, and 3) with SMX (197–1,575 μmol/L; μg/mL) and SMX metabolites (20–80 μmol/L). T-cell clones were incubated with SMX, SMX-NHOH, or SMX-NO and irradiated autologous B-lymphoblastoid cell lines for 48 hours to measure proliferation. Results are presented as the mean tritiated thymidine incorporation. Differences in replicate cultures at each antigen concentration were less than 15%. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 The response of SMX- and SMX metabolite–specific T-cell clones toward drug (metabolite)–pulsed antigen-presenting cells (A), antigen-presenting cells incubated with drug (metabolites) in the presence and absence of glutathione (B), and glutaraldehyde-fixed antigen-presenting cells (C). Results are presented as the mean ± SD tritiated thymidine incorporation. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Low-energy conformations and intermolecular forces associated with SMX-NO, nitrosobenzene, SMX, SD, and SP and the contribution of the different structural moieties. Calculated binding energies for SMX-NO and nitrosobenzene exclude the energy associated with the covalent interaction between the nitroso moiety and protein. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 The response of SMX- and SMX metabolite–responsive T-cell clones toward antigen-presenting cells incubated with drug (metabolites) in the presence and absence of glutathione (A), drug (metabolite)–pulsed antigen-presenting cells (B), and glutaraldehyde-fixed antigen-presenting cells (C). Results are presented as the mean ± SD tritiated thymidine incorporation. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 The response of T-cell clones to SMX, SD, and SP and their hydroxylamine and nitroso metabolites. Results are presented as the mean tritiated thymidine incorporation of representative T-cell clones. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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