Volume 4 Supplement 3

6th Drug Hypersensitivity Meeting (DHM 6)

Open Access

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

  • Lee Faulkner1,
  • Maike Lichtenfels1,
  • Philipp Esser2,
  • Stefan Martin2,
  • Ana Alfirevic1,
  • Munir Pirmohamed1,
  • Dean Naisbitt1 and
  • Kevin Park1
Clinical and Translational Allergy20144(Suppl 3):P114

https://doi.org/10.1186/2045-7022-4-S3-P114

Published: 18 July 2014

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 carbamazepine-induced 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 (SMX-NO)-specific T cells were generated from 6 individuals by priming naïve T-cells using drug-treated autologous dendritic cells. The responding cells were isolated using positive CD45RO magnetic bead selection. Naïve and SMX-NO specific T cells were analysed by serology for 24 TCR Vs and by RT-PCR spectra-typing of the CDR3 region.

Results

There was a marked expansion of TCR V4 and V9 in 5 donors, of TCR V11, V13.6 and V14 in 4 donors and of TCR V5.2 and V18 in 3 donors. We were able to show clonal expansion of these individual TCR Vs using CDR3 spectratyping analysis.

Conclusion

This data suggests that there may be a skewing of the T cell repertoire in SMX-NO specific responses.

Authors’ Affiliations

(1)
MRC Centre for Drug Safety Science, University of Liverpool
(2)
Allergy Research Group, University Medical Centre

Copyright

© Faulkner et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement