Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding

Staphylococcal enterotoxin B (SEB) simultaneously crosslinks MHC class II antigen and TCR, promoting proliferation of T cells and releasing a large number of toxic cytokines. In this report, we computationally examined the possibility of using a single-chain biparatopic bispecific antibody to target...

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Autores principales:	Ganggang Bai, Yanhong Ge, Yuhong Su, Shuo Chen, Xingcheng Zeng, Huixia Lu, Buyong Ma
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bispecific antibody staphylococcal enterotoxin B superantigen TCR antibody design molecular dynamics simulation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2c075474e8084923aca7398982076338
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spelling	oai:doaj.org-article:2c075474e8084923aca73989820763382021-11-30T12:24:06ZComputational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding1664-322410.3389/fimmu.2021.732938https://doaj.org/article/2c075474e8084923aca73989820763382021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.732938/fullhttps://doaj.org/toc/1664-3224Staphylococcal enterotoxin B (SEB) simultaneously crosslinks MHC class II antigen and TCR, promoting proliferation of T cells and releasing a large number of toxic cytokines. In this report, we computationally examined the possibility of using a single-chain biparatopic bispecific antibody to target SEB and prevent TCR binding. The design was inspired by the observation that mixing two anti-SEB antibodies 14G8 and 6D3 can block SEB-TCR activation, and we used 14G8-6D3-SEB tertiary crystal structure as a template. Twelve simulation systems were constructed to systematically examine the effects of the designed bispecific scFV MB102a, including isolated SEB, MB102a with different linkers, MB102a-SEB complex, MB102a-SEB-TCRβ complex, MB102a-SEB-TCR-MHC II complex, and MB102a-SEB-MHC II. Our all atom molecular dynamics simulations (total 18,900 ns) confirmed that the designed single-chain bispecific antibody may allosterically prevent SEB-TCRβ chain binding and inhibit SEB-TCR-MHC II formation. Subsequent analysis indicated that the binding of scFV to SEB correlates with SEB-TCR binding site motion and weakens SEB-TCR interactions.Ganggang BaiYanhong GeYuhong SuShuo ChenXingcheng ZengHuixia LuBuyong MaBuyong MaFrontiers Media S.A.articlebispecific antibodystaphylococcal enterotoxin BsuperantigenTCRantibody designmolecular dynamics simulationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bispecific antibody staphylococcal enterotoxin B superantigen TCR antibody design molecular dynamics simulation Immunologic diseases. Allergy RC581-607
spellingShingle	bispecific antibody staphylococcal enterotoxin B superantigen TCR antibody design molecular dynamics simulation Immunologic diseases. Allergy RC581-607 Ganggang Bai Yanhong Ge Yuhong Su Shuo Chen Xingcheng Zeng Huixia Lu Buyong Ma Buyong Ma Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
description	Staphylococcal enterotoxin B (SEB) simultaneously crosslinks MHC class II antigen and TCR, promoting proliferation of T cells and releasing a large number of toxic cytokines. In this report, we computationally examined the possibility of using a single-chain biparatopic bispecific antibody to target SEB and prevent TCR binding. The design was inspired by the observation that mixing two anti-SEB antibodies 14G8 and 6D3 can block SEB-TCR activation, and we used 14G8-6D3-SEB tertiary crystal structure as a template. Twelve simulation systems were constructed to systematically examine the effects of the designed bispecific scFV MB102a, including isolated SEB, MB102a with different linkers, MB102a-SEB complex, MB102a-SEB-TCRβ complex, MB102a-SEB-TCR-MHC II complex, and MB102a-SEB-MHC II. Our all atom molecular dynamics simulations (total 18,900 ns) confirmed that the designed single-chain bispecific antibody may allosterically prevent SEB-TCRβ chain binding and inhibit SEB-TCR-MHC II formation. Subsequent analysis indicated that the binding of scFV to SEB correlates with SEB-TCR binding site motion and weakens SEB-TCR interactions.
format	article
author	Ganggang Bai Yanhong Ge Yuhong Su Shuo Chen Xingcheng Zeng Huixia Lu Buyong Ma Buyong Ma
author_facet	Ganggang Bai Yanhong Ge Yuhong Su Shuo Chen Xingcheng Zeng Huixia Lu Buyong Ma Buyong Ma
author_sort	Ganggang Bai
title	Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
title_short	Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
title_full	Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
title_fullStr	Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
title_full_unstemmed	Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding
title_sort	computational construction of a single-chain bi-paratopic antibody allosterically inhibiting tcr-staphylococcal enterotoxin b binding
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2c075474e8084923aca7398982076338
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_version_	1718406611214532608

Computational Construction of a Single-Chain Bi-Paratopic Antibody Allosterically Inhibiting TCR-Staphylococcal Enterotoxin B Binding

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