Secretory component (SC) plays a central role in the mucosal immune system. It functions as an intergal membrane receptor, transcellular transporter, and protease inhibitor for its ligand polymeric IgA. A panel of monoclonal antibodies to human SC, characterized in our laboratories, offers a unique opportunity to study the immunobiology of SC. Our basic objective is to examine the structural characteristics which allow SC to function in its multiple specialized roles. Clinical studies will seek evidence for heterogeneity in size and structure of SC in different secretions and from different individuals. These studies may provide evidence for a modulatory role for SC and insight into alterations in SC metabolism in malignant epithelial cells. The SC from various secretions will be isolated by immunoaffinity chromatography and certain preparations will be modified by deglycosylation and limited and enzymatic proteolysis. Initially SDS polyacrylamide gel electrophoresis, HPLC and reaction with monoclonal antibodies will be used to characterize the size and epitopic structure of the products. Subsequently, amino acid and carbohydrate composition and amino acid sequence analysis will be determined for certain SC fragments. The in vitro function of the SC preparations will be assessed by evaluating polymeric IgA binding and inhibition of IgA proteolysis. Intracellular events will be examined using a colon carcinoma derived cell line. The intracellular pathway of SC will be followed by immunocytochemistry using monoclonal antibodies which distinguish the various physical forms of SC. Glycosylation will be inhibited with tunicamycin and attention focused on the role of carbohydrate in SC cellular function. Human IgG antibodies to SC will be used to probe the in vivo conformation of the receptor form of SC by comparing the spectrum of antibodies in the serum and secretions of individuals. A modulatory role for these antibodies will be tested in an in vitro model of SC function. Deliniation of the normal structure and function of SC will enhance our understanding of mucosal immunity and its control. Therapeutic applications of this knowledge may include the development of methods for targeting active or passive immunity or other therapeutic agents to the site of mucosal infections. The proposed studies may also elucidate alterations in SC metabolism in malignant epithelial cells which may allow direction of cytotoxic or chemotherapeutic agent selectively to these tumors.
