Title
The recombinant productions, characterizations and the interactions between Immunoglobulins type-M and the complement molecule C1: a textbook case for biophysical methods

 

Abstract
The classical pathway of the complement is one of the essential components of the immune system as it is responsible for modulating inflammation, regulating cellular and humoral responses, and clearing pathogens and altered-self. It is primarily triggered by the binding of the multimeric initiation C1 complex to antigen-bound immunoglobulins and leads to a long and amplifying proteolytic molecular pathway. Despite the discovery of the molecular actors more than a century ago, its molecular activation mechanisms have so far posed challenges for detailed characterizations, certainly because of the very complicated nature of the biomolecules and their interactions. Thanks to recent and tremendous technical improvements in biochemistry, biophysics, and structural biology, renewed interest has emerged and long-lasting and fundamental questions regarding antigens/Immunoglobulins/C1 complexes are started to be elucidated.
After briefly reviewing the progress made in the last few decades, I will present our work focused on the Immunoglobulins type-M (IgMs) and the C1 complex. Both are hetero-multimeric molecules with sophisticated assemblies, making their recombinant production a true challenge. Therefore, they serve as excellent case studies for applying lab protein engineering and for conducting extensive biophysical and in vitro functional characterizations to overcome bottlenecks. Our results not only exemplify the necessity of using different biophysical methods (ELISA, AUC, SEC-MALLS, Mass photometry, SPR, BLI…) available thanks to technical platforms but also pave the way for further biophysical and structural studies aimed at deciphering the detailed mechanisms of the complement activation. Additionally, they hold promise for future biotechnological or therapeutical tools developments.

Dr Jean-Baptiste REISER - Chargé de Recherche CNRS
Institut de Biologie Structurale - UMR 5075 (CNRS-CEA-UGA)
Complement, Antibodies and Infectious Diseases group
Integrated Structural Biology Grenoble - UAR 3518 - SPR/BLI platform
71 Avenue des Martyrs
CS 10090
38044 Grenoble cedex 9

Host : Benoît Odaert (CBMN - UMR 5248)