| RRC ID |
63605
|
| 著者 |
Shirayanagi T, Aoki S, Fujimori S, Watanabe K, Aida T, Hirasawa M, Kumagai K, Hoshino T, Ito K.
|
| タイトル |
Detection of Abacavir-Induced Structural Alterations in Human Leukocyte Antigen-B*57 : 01 Using Phage Display.
|
| ジャーナル |
Biol Pharm Bull
|
| 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 HLA complexes. We also identified an unreported structural change in HLA-B*57 : 01 using the phage display method, whereby abacavir increased the expression of peptide-deficient HLA-B*57 : 01 on the cell surface. These results suggest that phage display technology is a useful method for detecting structural changes in HLA complexes. This technology represents a potential novel strategy for predicting HLA-associated hypersensitivity reactions by drugs in pre-clinical studies.
|
| 巻・号 |
43(6)
|
| ページ |
1007-1015
|
| 公開日 |
2020-1-1
|
| DOI |
10.1248/bpb.b20-00102
|
| PMID |
32475910
|
| MeSH |
Anti-HIV Agents / pharmacology*
Antibodies / immunology
Cell Surface Display Techniques
Dideoxynucleosides / pharmacology*
HLA-B Antigens / chemistry*
HLA-B Antigens / genetics
HLA-B Antigens / immunology
HeLa Cells
Humans
|
| IF |
1.863
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa |
