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bioRxiv · 10.1101/557116

ILT7 activation and plasmacytoid dendritic cell response are governed by BST2 determinants that are structurally-distinct

Bego, M. G.·Miguet, N.·Laliberte, A.·Aschman, N.·Gerard, F.·Merakos, A. A.·Weissenhorn, W.·Cohen, E. A.
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Abstract

The interaction of the human pDC receptor ILT7 with its ligand, BST2, significantly regulates pDCs TLR-induced innate immune responses. This interaction has critical biological consequences, yet, its structural requirements are not fully characterized. The BST2 ectodomain can be divided in structurally and functionally distinct regions; while the coiled-coil region contains a newly-defined ILT7 binding surface, the N-terminal region appears to negatively modulate ILT7 activation. A stable BST2 homodimer binds to ILT7 but post-binding events associated to the unique BST2 coiled-coil plasticity are required to trigger receptor signaling. Hence, BST2 with an unstable or with a rigid coiled-coil fails to activate ILT7, whereas mutations in the N-terminal region enhance activation. Importantly, the biological relevance of these newly defined domains of BST2 is underscored by the identification of mutations with opposed potential to activate ILT7, which are selected under pathological malignant conditions.

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Bego, M. G., Miguet, N., Laliberte, A., Aschman, N., Gerard, F., Merakos, A. A., Weissenhorn, W., Cohen, E. A.. 2019-02-21. ILT7 activation and plasmacytoid dendritic cell response are governed by BST2 determinants that are structurally-distinct. https://doi.org/10.1101/557116

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