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Identification of a novel protective human monoclonal antibody, LXY8, that targets the key neutralizing epitopes of staphylococcal enterotoxin B.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Apr 16; Vol. 549, pp. 120-127. Date of Electronic Publication: 2021 Mar 02. - Publication Year :
- 2021
-
Abstract
- Staphylococcal enterotoxin B (SEB), one of the exotoxins produced by Staphylococcus aureus, is the key toxin that causes poisoning reactions and toxic shock syndrome. In the current research work, a novel human antibody named LXY8 was screened from a human phage display antibody library, and LXY8 blocked the interaction between SEB and the T cell receptor (TCR). The binding activity between LXY8 and SEB was 0.525 nM. Furthermore, LXY8 could effectively inhibit the SEB-induced activation of peripheral blood mononuclear cells and release of cytokines. In the BALB/c mouse model, LXY8 effectively neutralized SEB toxicity in vivo. Finally, based on computer-guided molecular modeling, we designed a series of SEB mutation sites; these sites facilitated the determination of the key residues (i.e. <superscript>176</superscript> EFNN <superscript>179</superscript> ) of SEB recognized by LXY8. The research revealed that the <superscript>176</superscript> EFNN <superscript>179</superscript> residues of SEB are important for specific antibody-antigen recognition. The results may be helpful for the development of antibody-based therapy for SEB-induced toxic shock syndrome.<br />Competing Interests: Declaration of competing interest Long L. Luo, Nai J. Hu, Chun X. Qiao, Jing Wang, Xin Y. Li, Jan N. Feng and Bei F. Shen have submitted patent applications pertaining to anti-SEB antibodies. The other authors declare no conflict of interest.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
CHO Cells
Cell Proliferation
Cell Surface Display Techniques
Cricetulus
Cytokines metabolism
Enterotoxins antagonists & inhibitors
Epitope Mapping
Female
Histocompatibility Antigens Class II metabolism
Humans
Mice, Inbred BALB C
Protein Binding
Receptors, Antigen, T-Cell metabolism
Mice
Antibodies, Bacterial analysis
Antibodies, Monoclonal analysis
Antibodies, Neutralizing analysis
Enterotoxins immunology
Epitopes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 549
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 33667709
- Full Text :
- https://doi.org/10.1016/j.bbrc.2021.02.057