Journal article
The structural basis of HLA-associated drug hypersensitivity syndromes
Immunological Reviews, Vol.250(1), pp.158-166
2012
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.
Details
- Title
- The structural basis of HLA-associated drug hypersensitivity syndromes
- Authors/Creators
- Y.A. Pompeu (Author/Creator) - University of FloridaJ.D. Stewart (Author/Creator) - University of FloridaS. Mallal (Author/Creator) - Murdoch UniversityE. Phillips (Author/Creator) - Murdoch UniversityB. Peters (Author/Creator) - La Jolla Institute for ImmunologyD.A. Ostrov (Author/Creator) - University of Florida
- Publication Details
- Immunological Reviews, Vol.250(1), pp.158-166
- Publisher
- Blackwell Publishing
- Identifiers
- 991005542947407891
- Copyright
- © 2012 John Wiley & Sons A/S.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology