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, and Gan, Samuel Ken-En (2021) Molecular insights of nickel binding to therapeutic antibodies as a possible new antibody superantigen. Frontiers in Immunology, 12. 676048.

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Abstract

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.

Item ID: 68931
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: allergy, glutamine, type I hypersensitivity, IgG1, IgE, nickel (II), antibody
Copyright Information: Copyright © 2021 Su, Lua, Poh, Ling, Yeo and Gan. 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.
Funders: Agency for Science, Technology and Research, Singapore (A*STAR)
Date Deposited: 18 Aug 2021 02:32
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320401 Allergy @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3206 Medical biotechnology > 320603 Medical molecular engineering of nucleic acids and proteins @ 20%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310299 Bioinformatics and computational biology not elsewhere classified @ 30%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
18 ENVIRONMENTAL MANAGEMENT > 1899 Other environmental management > 189999 Other environmental management not elsewhere classified @ 30%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 20%
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