Immune self-reactivity triggered by drug-modified HLA-peptide repertoire
Patricia T Illing, Julian P Vivian, Nadine L Dudek, Lyudmila Kostenko, Zhenjun Chen, Mandvi Bharadwaj, John J Miles, Lars Kjer-Nielsen, Stephanie Gras, Nicholas A Williamson, Scott R Burrows, Anthony W Purcell, Jamie Rossjohn, James McCluskey
NATURE | NATURE PUBLISHING GROUP | Published : 2012
Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles. However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in in..View full abstract
We thank R. Holdsworth and M. Diviney for support; N. Croft for discussions, and the staff at the MX2 beamline of the Australian synchrotron for assistance with data collection. This research was supported by a Program Grant from the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council (ARC). S. G. is supported by a Senior Fellowship from Monash University. A. W. P. is supported by an NHMRC Senior Research Fellowship; J.R. is supported by an NHMRC Australia Fellowship.