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Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common me...

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Autores principales: Su, Chinh Tran-To, Lua, Wai-Heng, Poh, Jun-Jie, Ling, Wei-Li, Yeo, Joshua Yi, Gan, Samuel Ken-En
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296638/
https://www.ncbi.nlm.nih.gov/pubmed/34305906
http://dx.doi.org/10.3389/fimmu.2021.676048
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author Su, Chinh Tran-To
Lua, Wai-Heng
Poh, Jun-Jie
Ling, Wei-Li
Yeo, Joshua Yi
Gan, Samuel Ken-En
author_facet Su, Chinh Tran-To
Lua, Wai-Heng
Poh, Jun-Jie
Ling, Wei-Li
Yeo, Joshua Yi
Gan, Samuel Ken-En
author_sort Su, Chinh Tran-To
collection PubMed
description The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes.
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spelling pubmed-82966382021-07-23 Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen Su, Chinh Tran-To Lua, Wai-Heng Poh, Jun-Jie Ling, Wei-Li Yeo, Joshua Yi Gan, Samuel Ken-En Front Immunol Immunology The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes. Frontiers Media S.A. 2021-07-08 /pmc/articles/PMC8296638/ /pubmed/34305906 http://dx.doi.org/10.3389/fimmu.2021.676048 Text en Copyright © 2021 Su, Lua, Poh, Ling, Yeo and Gan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Su, Chinh Tran-To
Lua, Wai-Heng
Poh, Jun-Jie
Ling, Wei-Li
Yeo, Joshua Yi
Gan, Samuel Ken-En
Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title_full Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title_fullStr Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title_full_unstemmed Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title_short Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
title_sort molecular insights of nickel binding to therapeutic antibodies as a possible new antibody superantigen
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296638/
https://www.ncbi.nlm.nih.gov/pubmed/34305906
http://dx.doi.org/10.3389/fimmu.2021.676048
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