| The structural basis of HLA-associated drug hypersensitivity syndromes. | |
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MedLine Citation:
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PMID: 23046128 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yuri A Pompeu; Jon D Stewart; Simon Mallal; Elizabeth Phillips; Bjoern Peters; David A Ostrov |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Immunological reviews Volume: 250 ISSN: 1600-065X ISO Abbreviation: Immunol. Rev. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7702118 Medline TA: Immunol Rev Country: England |
Other Details:
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Languages: eng Pagination: 158-66 Citation Subset: IM |
Copyright Information:
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© 2012 John Wiley & Sons A/S. |
Affiliation:
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Department of Chemistry, University of Florida, Gainesville, FL, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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