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Spatio temporal regulation of antigen presentation and cell migration

The immune system is constituted by different cell populations, which circulate between lymphoid organs and peripheral tissues as a result of their high migratory capacity. We have shown that Antigen (Ag) processing and migration... ver más

30/11/2015

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2M€

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2015-11-30 No tenemos la información de la convocatoria

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INSTITUT CURIE No se ha especificado una descripción o un objeto social para esta compañía.

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Presupuesto del proyecto 2M€

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Descripción del proyecto The immune system is constituted by different cell populations, which circulate between lymphoid organs and peripheral tissues as a result of their high migratory capacity. We have shown that Antigen (Ag) processing and migration of Ag Presenting Cells (APCs) are co-regulated by a protein complex that contains the MHC class II-associated Invariant Chain (Ii) and the actin-based motor protein Myosin II. While the association between Ii and Myosin II promotes Ag processing for presentation onto MHC class II molecules, it impairs APC motility, suggesting that the use of common regulators enables APCs to coordinate Ag processing and cell migration in time and space. We here propose an innovative multi-disciplinary approach, at the interface of immunology, cell biology and biophysics, aimed to unravel the fundamental mechanisms allowing the coordination of Ag processing and APC migration and to evaluate their impact on the adaptive immune response. Our specific aims stand as follows: (1) Combine two-photon microscopy in living tissues and micro-fabricated tools to highlight the molecular mechanisms by which the Ii-Myosin II complex couples Ag processing and cell migration in APCs. (2) Use mouse models to provide a quantitative analysis of the impact of the coordination of Ag processing and APC migration on the onset of the adaptive immune response in vivo. (3) Extend this analysis by performing a genetic screen to identify the molecules and cellular parameters that are critical for coordination of Ag processing and APC migration. The molecular mechanisms that regulate cell motility being conserved between the different types of leukocytes, we foresee that our results will shed light on the fundamental immunological question of how immune cells in general regulate their individual effector function in time and space.

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