Skewing of the TCR V repertoire in SMX‐NO specific T cell responses

Abstract

Background A role for drug-specific T cells has been demonstrated in many instances of drug hypersensitivity. In the case of -lactam antibiotics, such as flucloxacillin, we have shown that drug-protein conjugates are present in the plasma of all patients treated with this antibiotic, however only a small subset of patients develop hypersensitivity. Similarly, when a strong HLA association to drug hypersensitivity has been demonstrated such as for abacavir, not all patients with the risk allele will develop a hypersensitivity reaction. The mechanism underlying this variation in susceptibility is not fully understood. In carbamazepineinduced Stevens Johnson syndrome it is known that only patients with both the HLA risk allele and T cells with a specific TCR V will develop a reaction. This shows that an individual’s T cell repertoire may confer some susceptibility to drug hypersensitivity. Method In initial experiments, SMX-NO-specific CD4+ clones were generated from hypersensitive patients and analysed for TCR V expression. Nitroso sulfamethoxazole (SMXNO)-specific T cells were generated from 6 individuals by priming naive T-cells using drug-treated autologous dendritic cells. The responding cells were isolated using positive CD45RO magnetic bead selection. Naive and SMX-NO specific T cells were analysed by serology for 24 TCR Vs and by RT-PCR spectra-typing of the CDR3 region.