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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8296638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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