PMID- 32475910
OWN - NLM
STAT- MEDLINE
DCOM- 20210121
LR  - 20210121
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 43
IP  - 6
DP  - 2020
TI  - Detection of Abacavir-Induced Structural Alterations in Human Leukocyte 
      Antigen-B*57 : 01 Using Phage Display.
PG  - 1007-1015
LID - 10.1248/bpb.b20-00102 [doi]
AB  - 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.
FAU - Shirayanagi, Tomohiro
AU  - Shirayanagi T
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Aoki, Shigeki
AU  - Aoki S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Fujimori, Sota
AU  - Fujimori S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Watanabe, Kenji
AU  - Watanabe K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Aida, Tetsuo
AU  - Aida T
AD  - Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
FAU - Hirasawa, Makoto
AU  - Hirasawa M
AD  - Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., 
      Ltd.
FAU - Kumagai, Kazuyoshi
AU  - Kumagai K
AD  - Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
FAU - Hoshino, Tyuji
AU  - Hoshino T
AD  - Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, 
      Chiba University.
FAU - Ito, Kousei
AU  - Ito K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Antibodies)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B57 antigen)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Anti-HIV Agents/*pharmacology
MH  - Antibodies/immunology
MH  - Cell Surface Display Techniques
MH  - Dideoxynucleosides/*pharmacology
MH  - HLA-B Antigens/*chemistry/genetics/immunology
MH  - HeLa Cells
MH  - Humans
OTO - NOTNLM
OT  - adverse drug reaction
OT  - human leukocyte antigen
OT  - phage display
EDAT- 2020/06/02 06:00
MHDA- 2021/01/22 06:00
CRDT- 2020/06/02 06:00
PHST- 2020/06/02 06:00 [entrez]
PHST- 2020/06/02 06:00 [pubmed]
PHST- 2021/01/22 06:00 [medline]
AID - 10.1248/bpb.b20-00102 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2020;43(6):1007-1015. doi: 10.1248/bpb.b20-00102.