Journal article
HLA restriction of carbamazepine-specific T-cell clones from an HLA-A*31:01-positive hypersensitive patient
M Lichtenfels, J Farrell, MO Ogese, CC Bell, S Eckle, J McCluskey, BK Park, A Alfirevic, DJ Naisbitt, M Pirmohamed
Chemical Research in Toxicology | Published : 2014
DOI: 10.1021/tx400460w
Abstract
HLA-A*31:01 is associated with carbamazepine (CBZ) hypersensitivity in Caucasian and Japanese populations. Herein, we show that HLA-A*31:01+ restricted the activation of carbamazepine-specific CD8+ T-cells, which provides an immunological basis for the genetic association. Furthermore, CD4+ T-cells were activated with carbamazepine in a HLA-DRB1*04:04-restricted manner, indicating that a common HLA haplotype may contribute to the multiclonal T-cell response seen in European patients with CBZ hypersensitivity. © 2014 American Chemical Society.
Grants
Awarded by Department of Health
Funding Acknowledgements
This work was funded from the European Union's Seventh Framework Programme FP7/2007-2013 under grant agreement number 238132 and the Centre for Drug Safety Science supported by the Medical Research Council (G0700654). M.P. is a NIHR Senior Investigator and is funded by the NHS Chair of Pharmacogenetics from the UK Department of Health.