TRANSCELLULAR TRANSPORT OF IMMUNOGLOBULINS

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Further studies are proposed to detial the cellular mechanisms whereby maternal immunoglobulin G (IgG) is selectively transferred across the intestinal epithelium of neonatal rats and mice by receptor-mediated endocytosis. Individual projects are proposed to evaluate the consequences of both normal and abnormal transport function. (1) The movement of membrane components and sorting of vesicle contents will be analyzed during selective IgG endocytosis by intestinal cells in situ using a variety of ultrastructural tracers including IgG-tracer conjugates, cationic ferritin, labeled lectins and anti-brush border antibody conjugates. Possible effects of lysosomal and other metabolic inhibitors will be investigated. (2) The pH-dependent binding of labled IgG to its membrane receptors will be studied using both ultrastructural and 125-I assays with isolated brush borders and intact cells. Effects of assay conditions and various treatments on the association constant and number of binding sites will be evaluated. (3) Factors that might influence the movement of receptors on the apical cell surface and the formation of endocytic vesicles will be investigated using isolated brush borders and intestinal cell in vitro. (4) The ultrastructural mechanism of entry into the neonatal mouse of mammary tumor virus, a pathogen known to be transferred across the intestine during the suckling period, will be studied. The possible role of specific antibody in transport and infection will be evaluated.