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Interaction Studies of Hexameric and Pentameric IgMs with Serum-Derived C1q and Recombinant C1q Mimetics.
John, Maria Magdalena; Hunjadi, Monika; Hawlin, Vanessa; Reiser, Jean-Baptiste; Kunert, Renate.
Afiliación
  • John MM; Institute of Animal Cell Technology and Systems Biology, Department of Biotechnology, BOKU University, Muthgasse 11, 1190 Vienna, Austria.
  • Hunjadi M; Institute of Animal Cell Technology and Systems Biology, Department of Biotechnology, BOKU University, Muthgasse 11, 1190 Vienna, Austria.
  • Hawlin V; Institute of Animal Cell Technology and Systems Biology, Department of Biotechnology, BOKU University, Muthgasse 11, 1190 Vienna, Austria.
  • Reiser JB; Institut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000 Grenoble, France.
  • Kunert R; Institute of Animal Cell Technology and Systems Biology, Department of Biotechnology, BOKU University, Muthgasse 11, 1190 Vienna, Austria.
Life (Basel) ; 14(5)2024 May 17.
Article en En | MEDLINE | ID: mdl-38792658
ABSTRACT
The interaction between IgM and C1q represents the first step of the classical pathway of the complement system in higher vertebrates. To identify the significance of particular IgM/C1q interactions, recombinant IgMs were used in both hexameric and pentameric configurations and with two different specificities, along with C1q derived from human serum (sC1q) and two recombinant single-chain variants of the trimeric globular region of C1q. Interaction and complement activation assays were performed using the ELISA format, and bio-layer interferometry measurements to study kinetic behavior. The differences between hexameric and pentameric IgM conformations were only slightly visible in the interaction assay, but significant in the complement activation assay. Hexameric IgM requires a lower concentration of sC1q to activate the complement compared to pentameric IgM, leading to an increased release of C4 compared to pentameric IgM. The recombinant C1q mimetics competed with sC1q in interaction assays and were able to inhibit complement activation. The bio-layer interferometry measurements revealed KD values in the nanomolar range for the IgM/C1q interaction, while the C1q mimetics exhibited rapid on and off binding rates with the IgMs. Our results make C1q mimetics valuable tools for developing recombinant C1q, specifically its variants, for further scientific studies and clinical applications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Life (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Life (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Suiza