Drug-modified peptide:Major Histocompatibility Complex (Drug-pMHC)

The drug-modified peptide:Major Histocompatibility Complex (MHC) is a molecular assembly formed when a drug or its metabolite interacts with an endogenous peptide and an MHC molecule. This interaction can occur through covalent bonding (hapten hypothesis), where the drug modifies a protein that is subsequently processed into peptides, or through non-covalent binding directly to the MHC binding groove or the peptide-MHC complex (p-i model and altered peptide repertoire model) (Illing et al., Nature 2012; Ostrov et al., PNAS 2012). These complexes are recognized by T-cell receptors (TCRs) as foreign "neoantigens," triggering a potent immune response (Pichler, Ann Intern Med 2003). This mechanism is the underlying cause of various drug-induced hypersensitivity reactions (DIHRs), including severe cutaneous adverse reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (Chung et al., Nature 2004). Understanding these complexes is crucial for predicting drug toxicity and developing safer pharmaceuticals, particularly in patients carrying specific HLA risk alleles (Yun et al., J Allergy Clin Immunol 2016). While the complex itself is the driver of pathology, it serves as a target for diagnostic assays and potential therapeutic interventions aimed at modulating T-cell responses (White et al., J Allergy Clin Immunol 2015).

Other names

Drug-peptide-MHC complexHapten-peptide-MHC complexDrug-induced neoantigenDrug-MHC complex

T-cell receptor recognition of drug-induced neoantigens presented by MHC molecules, leading to cytotoxic T-lymphocyte activation and cytokine release.