Drug hapten-specific T-cell activation: Current status and unanswered questions

Adair, Kareena ORCID: 0000-0001-9884-2094, Meng, Xiaoli ORCID: 0000-0002-7774-2075 and Naisbitt, Dean J
(2021) Drug hapten-specific T-cell activation: Current status and unanswered questions. PROTEOMICS, 21 (17-18). e2000267-.

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Drug haptens are formed from the irreversible, covalent binding of drugs to nucleophilic moieties on proteins, which can warrant adverse reactions in the body including severe delayed-type, T-cell mediated, drug hypersensitivity reactions (DHRs). While three main pathways exist for the activation of T-cells in DHRs, namely the hapten model, the pharmacological interaction model and the altered peptide repertoire model, the exact antigenic determinants responsible have not yet been defined. In recent years, progress has been made using advanced mass spectrometry-based proteomic methods to identify protein carriers and characterise the structure of drug-haptenated proteins. Since genome-wide association studies discovered a link between human leukocyte antigens (HLA) and an individual's susceptibility to DHRs, much effort has been made to define the drug-associated HLA ligands driving T-cell activation, including the elution of natural HLA peptides from HLA molecules and the generation of HLA-binding peptides. In this review, we discuss our current methodology used to design and synthesise drug-modified HLA ligands to investigate their immunogenicity using T-cell models, and thus their implication in drug hypersensitivity.

Item Type: Article
Uncontrolled Keywords: drug hypersensitivity, haptenated HLA ligands, LC-MS, MS, peptide synthesis, T-cell activation
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Apr 2021 15:53
Last Modified: 18 Jan 2023 22:53
DOI: 10.1002/pmic.202000267
Open Access URL: https://doi.org/10.1002/pmic.202000267
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3119176