Detection of Abacavir-Induced Structural Alterations in Human Leukocyte Antigen-B*57  : 01 Using Phage Display.

Detection of Abacavir-Induced Structural Alterations in Human Leukocyte Antigen-B*57 : 01 Using Phage Display. Biol Pharm Bull. 2020;43(6):1007-1015 Authors: Shirayanagi T, Aoki S, Fujimori S, Watanabe K, Aida T, Hirasawa M, Kumagai K, Hoshino T, Ito K Abstract The interaction of human leukocyte antigen (HLA) with specific drugs is associated with delayed-type hypersensitivity reactions, which cause severe cutaneous toxicity. Such interactions induce structural alterations in HLA complexes via several different mechanisms such as the hapten theory, p-i concept, and altered peptide repertoire model, leading to the activation of cytotoxic T cells. To date, comprehensive detection of such structural alterations in preclinical studies has been difficult. Here, we evaluated structural alterations in HLA complexes focusing on the interaction between the HLA-B*57 : 01 allele and abacavir (an anti-human immunodeficiency virus drug), representing a model of abacavir hypersensitivity syndrome induced by changes in the peptide repertoire on the HLA molecule. We employed a phage display method using a commercially available antibody library to screen specific phage antibodies able to recognize HLA-B*57 : 01. The affinity of selected phage antibodies increased because of structural alterations in HLA-B*57 : 01 following exposure to abacavir, indicating that specific phage antibodies can identify drug-mediated structural changes in...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research