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Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency

Anti-interferon gamma autoantibodies (anti-IFN-gamma autoAbs) neutralize the IFN-gamma-mediated functions, contributing to immunodeficiency. A particular autoAb in patient serum had been previously demonstrated to recognize the same determinant on IFN-gamma as the neutralizing anti-IFN-gamma monoclo...

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Main Authors: Yasamut, Umpa, Wisitponchai, Tanchanok, Lee, Vannajan Sanghiran, Yamabhai, Montarop, Rangnoi, Kuntalee, Thongkum, Weeraya, Chupradit, Koollawat, Tayapiwatana, Chatchai
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Published: Nature Research 2022
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Q Science (General)
Online Access:http://eprints.um.edu.my/42817/
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spelling my.um.eprints.428172023-08-29T01:47:27Z http://eprints.um.edu.my/42817/ Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency Yasamut, Umpa Wisitponchai, Tanchanok Lee, Vannajan Sanghiran Yamabhai, Montarop Rangnoi, Kuntalee Thongkum, Weeraya Chupradit, Koollawat Tayapiwatana, Chatchai Q Science (General) Anti-interferon gamma autoantibodies (anti-IFN-gamma autoAbs) neutralize the IFN-gamma-mediated functions, contributing to immunodeficiency. A particular autoAb in patient serum had been previously demonstrated to recognize the same determinant on IFN-gamma as the neutralizing anti-IFN-gamma monoclonal antibody clone B27 (B27 mAb). This study explored the epitope recognized by B27 mAb. The specific peptide sequence recognized by B27 mAb, TDFLRMMLQEER, was retrieved from a phage display random peptide library. Sequence alignment and homology modeling demonstrated that the queried phage peptide sequence and structure were similar to amino acids at position 27-40 (TLFLGILKNWKEES) of the human IFN-gamma. This determinant resides in the contact surface of IFN-gamma and interferon gamma receptor 1. To elucidate the crucial amino acids, mutations were introduced by substituting T27 and T27F29L30 with alanine or deleting the amino acid residues T27-L33. The binding of B27 mAb to IFN-gamma T27A using western blotting was lesser than that to wild-type. The interaction with triple mutant and T27-L33 deletion mutant using western blotting and sandwich ELISA was abolished. The finding demonstrated that T27, F29, and L30 are critical residues in the B27 antigenic determinant. Identification of the functional domain of IFN-gamma decrypted the relevance of neutralizing autoAb in adult-onset immunodeficiency. Nature Research 2022-05 Article PeerReviewed Yasamut, Umpa and Wisitponchai, Tanchanok and Lee, Vannajan Sanghiran and Yamabhai, Montarop and Rangnoi, Kuntalee and Thongkum, Weeraya and Chupradit, Koollawat and Tayapiwatana, Chatchai (2022) Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency. Scientific Reports, 12 (1). ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-022-11774-9 <https://doi.org/10.1038/s41598-022-11774-9>. 10.1038/s41598-022-11774-9
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic Q Science (General)
spellingShingle Q Science (General)
Yasamut, Umpa
Wisitponchai, Tanchanok
Lee, Vannajan Sanghiran
Yamabhai, Montarop
Rangnoi, Kuntalee
Thongkum, Weeraya
Chupradit, Koollawat
Tayapiwatana, Chatchai
Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
description Anti-interferon gamma autoantibodies (anti-IFN-gamma autoAbs) neutralize the IFN-gamma-mediated functions, contributing to immunodeficiency. A particular autoAb in patient serum had been previously demonstrated to recognize the same determinant on IFN-gamma as the neutralizing anti-IFN-gamma monoclonal antibody clone B27 (B27 mAb). This study explored the epitope recognized by B27 mAb. The specific peptide sequence recognized by B27 mAb, TDFLRMMLQEER, was retrieved from a phage display random peptide library. Sequence alignment and homology modeling demonstrated that the queried phage peptide sequence and structure were similar to amino acids at position 27-40 (TLFLGILKNWKEES) of the human IFN-gamma. This determinant resides in the contact surface of IFN-gamma and interferon gamma receptor 1. To elucidate the crucial amino acids, mutations were introduced by substituting T27 and T27F29L30 with alanine or deleting the amino acid residues T27-L33. The binding of B27 mAb to IFN-gamma T27A using western blotting was lesser than that to wild-type. The interaction with triple mutant and T27-L33 deletion mutant using western blotting and sandwich ELISA was abolished. The finding demonstrated that T27, F29, and L30 are critical residues in the B27 antigenic determinant. Identification of the functional domain of IFN-gamma decrypted the relevance of neutralizing autoAb in adult-onset immunodeficiency.
format Article
author Yasamut, Umpa
Wisitponchai, Tanchanok
Lee, Vannajan Sanghiran
Yamabhai, Montarop
Rangnoi, Kuntalee
Thongkum, Weeraya
Chupradit, Koollawat
Tayapiwatana, Chatchai
author_facet Yasamut, Umpa
Wisitponchai, Tanchanok
Lee, Vannajan Sanghiran
Yamabhai, Montarop
Rangnoi, Kuntalee
Thongkum, Weeraya
Chupradit, Koollawat
Tayapiwatana, Chatchai
author_sort Yasamut, Umpa
title Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
title_short Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
title_full Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
title_fullStr Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
title_full_unstemmed Determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
title_sort determination of a distinguished interferon gamma epitope recognized by monoclonal antibody relating to autoantibody associated immunodeficiency
publisher Nature Research
publishDate 2022
url http://eprints.um.edu.my/42817/
_version_ 1776247436149260288
score 13.211869

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