Control of antigen processing by Fc receptors. (360G-Wellcome-084953_Z_08_Z)
My proposal seeks to understand how Fcgamma receptors (FcgRs) control antigen processing by dendritic cells and macrophages. Since FcgR subtypes are variably expressed, have different binding affinities for different IgG subclasses and lead to fundamentally distinct patterns of intracellular trafficking and processing, it is not understood how, for a given repertoire of expressed FcgR, a specific antigen will be processed and what programme of effector functions will be triggered. My first key g oal will be to systematically define functional outcomes (binding and internalisation, antigen degradation and presentation) for ligand-receptor combinations using a receptor expression library in U937 cells expressing 90 different patterns of receptor subtype and disease-associated polymorphisms. Findings will then be confirmed using primary cells from healthy volunteers. I will then define the critical signal transduction events responsible for determining immunogenic and tolerogenic antigen p rocessing focussing on 1) the effect of receptor membrane sub-localisation on receptor function and cellular behaviour and 2) the role of macro-autophagy in modulating or possibly mediating FcgR-triggered intracellular antigen trafficking.
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Grant Details
Amount Awarded | 1572010 |
Applicant Surname | Floto |
Approval Committee | Clinical Interview Committee |
Award Date | 2008-06-05T00:00:00+00:00 |
Financial Year | 2007/08 |
Grant Programme: Title | Senior Research Fellowship Clinical |
Internal ID | 084953/Z/08/Z |
Lead Applicant | Prof Andres Floto |
Partnership Value | 1572010 |
Planned Dates: End Date | 2014-11-30T00:00:00+00:00 |
Planned Dates: Start Date | 2008-12-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Prof David Rubinsztein, Prof Paul Lehner |