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ß+ T Cell Clones1
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland
Drugs like sulfamethoxazole (SMX) or lidocaine can be presented to
specific human 
ß+ T cell clones (TCC) by undergoing a
noncovalent association with MHC-peptide complexes on HLA-matched APCs.
For a better understanding of the molecular basis of the recognition of
such drugs by specific TCC, we investigated 1) the fine specificity of
the recognizing TCR, 2) the dose-response relationship for the
induction of proliferation or cytokine production, and 3) the mechanism
of TCR triggering. For that purpose, we tested the reactivity of 11
SMX-specific CD4+ TCC and 2 SMX-specific CD8+
TCC to a panel of 13 different sulfonamide derivatives bearing the same
core structure. Five of 13 clones recognized only SMX, while all other
clones were responding to as many as 6 different compounds. Some of the
compounds needed up to two orders of magnitude higher concentrations
than SMX to stimulate TCC, thereby displaying features of weak
agonists. Different clones showed clear differences in the minimal drug
concentration required for the induction of a proliferative response.
Therefore, weaker or stronger agonistic properties were not a
characteristic of a given sulfonamide derivative but rather an
intrinsic property of the reacting TCR. Finally, the number of
down-regulated TCRs was a logarithmic function of the ligand
concentration, implicating that specific T cells were activated by
serial TCR engagement. Our data demonstrate that, despite the special
way of presentation, nonpeptide Ag like drugs appear to interact with
the TCR of specific T cells in a similar way as peptide
Ags.
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