Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

The structural basis of HLA-associated drug hypersensitivity syndromes

Pompeu, Y.A., Stewart, J.D., Mallal, S., Phillips, E., Peters, B. and Ostrov, D.A. (2012) The structural basis of HLA-associated drug hypersensitivity syndromes. Immunological Reviews, 250 (1). pp. 158-166.

Link to Published Version: http://dx.doi.org/10.1111/j.1600-065X.2012.01163.x
*Subscription may be required

Abstract

Recent data suggest alternative mechanisms that promote human leukocyte antigen (HLA)-associated drug syndromes. Hypersensitive responses have been attributed to drug interactions with HLA molecules, peptides presented by HLA molecules and T-cell antigen receptors. Definition of an increasing number of HLA-associated drug syndromes suggests that polymorphism in the antigen-binding cleft residues influence recognition of specific drugs. Recent data demonstrate that small molecule drugs bind within the antigen-binding cleft of HLA in a manner that alters the repertoire of HLA-bound peptide ligands. This drug recognition mechanism permits presentation of self-peptides to which the host has not been tolerized. This altered repertoire mechanism is analogous to massive polyclonal T-cell responses occurring in mismatched HLA organ transplantation in which the drug in effect creates a novel HLA allele. Alteration of the self-peptide repertoire by HLA-binding small molecules may be the mechanistic basis for a diverse set of deleterious T-cell responses since the antigen-binding cleft has structural features that are compatible with binding drug-like small molecules. Small molecule drugs that bind elements of the trimolecular complex (T-cell receptor, peptide, and HLA) may cause short- and long-term adverse effects by a diverse set of mechanisms.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Blackwell Publishing
Copyright: © 2012 John Wiley & Sons A/S.
URI: http://researchrepository.murdoch.edu.au/id/eprint/11284
Item Control Page Item Control Page