Mucosal surfaces are the major areas of the body that are under continuous assault by environmental antigens and pathogens. This onslaught provokes antibody responses in which IgA is the predominant isotype. However, the mechanism whereby this antibody provides protection is incompletely understood. Our current knowledge suggests that human phagocytic cells play a significant role in the protection of mucosal areas via Fc receptors for IgA. The cells play a significant role in the protection of mucosal areas via Fc receptors for IgA. The principal investigator recently produced an anti-IgA receptor monoclonal antibody that will be a valuable tool in analyzing the role of these receptors. This antibody has played a key role in a collaboration with Dr. Maliszewski, in which a cDNA sequence for the IgA receptor was cloned. The antibody and cDNA reagents offer a unique and exciting opportunity to clarify the nature and function of these receptors. The proposed studies will investigate the modulation, function, and structure of IgA receptors in depth. The augmentation of receptor expression by cytokines will be examined both at the cell surface and RNA level, the latter studies using a probe derived from the cDNA encoding the human IgA receptor. Functional studies employing anti-IgA receptor heteroantibodies will explore the ability of phagocytes to kill bacteria, perform phagocytosis, and to secrete bactericidal agents and mediators of immune regulation. The ability of the cloned receptor to support function will also be assessed. Other studies will analyse and compare the structure and biochemistry of naturally occurring and cloned IgA receptors. Should the existence of receptor isoforms be confirmed, their detailed structure will be examined by recombinant DNA techniques. Receptor biosynthesis will also be examined. These experiments will be complemented by immunohistochemical studies using the anti-IgA receptor mAb to visualize tissue distribution of IgA receptors. It is anticipated that these studies will greatly advance our understanding both of the basic biology of IgA receptors and the role they play in mucosal protection and in pathological conditions.