Noncovalent interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions

Gerber, Basil O; Pichler, Werner J (2006). Noncovalent interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions. AAPS journal, 8(1), E160-5. Arlington, Va.: Springer-Verlag 10.1208/aapsj080119

[img]
Preview
Text
12248_2008_Article_81160.pdf - Published Version
Available under License Publisher holds Copyright.

Download (186kB) | Preview

Drug-induced hypersensitivity reactions are instructive examples of immune reactions against low molecular weight compounds. Classically, such reactions have been explained by the hapten concept, according to which the small antigen covalently modifies an endogenous protein; recent studies show strong associations of several HLA molecules with hypersensitivity. In recent years, however, evidence has become stronger that not all drugs need to bind covalently to the major histocompatibility complex (MHC)-peptide complex in order to trigger an immune response. Rather, some drugs may bind reversibly to the MHC or possibly to the T-cell receptor (TCR), eliciting immune reactions akin to the pharmacological activation of other receptors. While the exact mechanism is still a matter of debate, noncovalent drug presentation clearly leads to the activation of drug-specific T cells. In some patients with hypersensitivity, such a response may occur within hours of even the first exposure to the drug. Thus, the reaction to the drug may not be the result of a classical, primary response but rather be mediated by existing, preactivated T cells that display cross-reactivity for the drug and have additional (peptide) specificity as well. In this way, certain drugs may circumvent the checkpoints for immune activation imposed by the classical antigen processing and presentation mechanisms, which may help to explain the idiosyncratic nature of many drug hypersensitivity reactions.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Gerber, Basil Oliver and Pichler, Werner Joseph

ISSN:

1550-7416

ISBN:

16584124

Publisher:

Springer-Verlag

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:46

Last Modified:

24 Oct 2019 03:04

Publisher DOI:

10.1208/aapsj080119

PubMed ID:

16584124

Web of Science ID:

000236804800019

BORIS DOI:

10.7892/boris.19113

URI:

https://boris.unibe.ch/id/eprint/19113 (FactScience: 1489)

Actions (login required)

Edit item Edit item
Provide Feedback