Interaction Studies of Hexameric and Pentameric IgMs with Serum-Derived C1q and Recombinant C1q Mimetics - Groupe Complément, anticorps et maladies infectieuses / Complement, antibodies and infectious disease Group (IBS-CAID) Accéder directement au contenu
Article Dans Une Revue Life Année : 2024

Interaction Studies of Hexameric and Pentameric IgMs with Serum-Derived C1q and Recombinant C1q Mimetics

Résumé

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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hal-04618136 , version 1 (20-06-2024)

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Maria Magdalena John, Monika Hunjadi, Vanessa Hawlin, Jean-Baptiste Reiser, Renate Kunert. Interaction Studies of Hexameric and Pentameric IgMs with Serum-Derived C1q and Recombinant C1q Mimetics. Life, 2024, 14 (5), pp.638. ⟨10.3390/life14050638⟩. ⟨hal-04618136⟩
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