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Systèmes effecteurs de l'immunité innée : reconnaissance et voies de signalisation.
- Etude structurale des propriétés de reconnaissance des ficolines et du C1q
- Etude cellulaire du rôle de la protéine ELMO1 dans l'élimination des cellules apoptotiques

Abstract : The innate immune system triggers inflammatory defences against pathogens or dangerous cells but is also involved in the tolerogenic removal of apoptotic cells. Target recognition is mediated by a wide range of soluble or membrane proteins. Among them are the essential complement recognition proteins: mannose-binding lactin, C1q and ficolins. Whereas the structural recognition properties of mannose-binding lectin BL have been extensively studied, the corresponding properties of ficolins and C1q with their ligands had to be deciphered at the atomic level. This was thus the aim of the first part of the project presented here. This was experimentally studied through the X-ray structural analysis of the corresponding ficolins and C1q recognition domains, alone or in complex with several cognate ligands. We have shown that H- and M- ficolins possess only one binding site, conserved among fibrinogen-like domains. This conserved site does not seem to be active in L-ficolin, but new binding sites were discovered instead, defining a larger surface of recognition more suitable to the binding of elongated polymers. Interestingly, we also found a new binding site for phosphoserine in C1q. We also provided evidence for two unique properties of M-ficolin: the binding of Neu5Ac, a classical self-marker, and a pH-dependent conformational switch of the binding site. As recognition properties of a few recognition proteins do not explain the different behaviour of immune cells with altered-self debris, we initiated a new project to understand signalling pathways in phagocytes during apoptotic cells removal. Many data suggest that a GEF complex: ELMO/DOCK is common to many pathways activated by apoptotic cells recognition and is also a point of regulation. My work in this second project was to initiate the setup of cellular tools to study the behaviour of this complex in different model cell lines. I developed quantitative phagocytic tests and also tools for detection and surexpression of ELMO1 in different cells lines. We also observed the re-localisation of cellular ELMO1 in the phagocytic cup.
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https://tel.archives-ouvertes.fr/tel-00404006
Contributor : Virginie Garlatti <>
Submitted on : Wednesday, July 15, 2009 - 10:24:03 AM
Last modification on : Tuesday, July 27, 2021 - 9:06:02 AM
Long-term archiving on: : Tuesday, June 15, 2010 - 6:42:40 PM

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  • HAL Id : tel-00404006, version 1

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Virginie Garlatti. Systèmes effecteurs de l'immunité innée : reconnaissance et voies de signalisation.
- Etude structurale des propriétés de reconnaissance des ficolines et du C1q
- Etude cellulaire du rôle de la protéine ELMO1 dans l'élimination des cellules apoptotiques. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00404006⟩

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