The objective of the proposed research is to describe in molecular terms how immunoglobulins are transported from a pregnant or nursing mammal to her unborn or newborn offspring. The acquisition of maternal antibodies is essential for immunologic defense, although autoantibodies and immune complexes of live pathogens are potentially harmful to the neonate. We have two major goals. The first is to elucidate the molecular mechanism of intestinal IgG uptake in the suckling rat by an Fc receptor called FcRn (for neonate). This system will be used as a model for intracellular protein trafficking and specifically for the transmission of IgG across the human placenta. To identify and characterized charcterize the Fc receptor(s) that mediate placental transport of IgG is our second goal.
Our specific aims are to: 1. Develop a monolayer cell culture model for transcytosis of IgG by FcRn. 2. Relate the structure of FcRn to its functions by measuring the properties of modified forms of the receptor in the cell culture model. 3. Study how the gene(s) that code for FcRn is (are) organized. 4. Study how the production of FcRn is regulated during development. 5. Identify and characterize by molecular cloning FcRs that transport IgG across human placenta.
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