CHARACTERIZATION OF SUB-EPITHELIAL MATRIX ANTIGENS

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The basement membrane zone underlying the squamous epithelium of external tissues is ultrastructurally more complex than basement membrane zones of other tissues. In addition to lamina densa, these regions contain additional cellular elements such as the hemidesmosomes of the basal cells, anchoring filaments between the hemidesmosomes and the lamina densa, anchoring fibrils which appear to connect the lamina densa with the underlying connective tissue, and oxytalan fibers which may mediate the interaction of elastic elements with the lamina densa. The diseases of bullous pemphigoid and epidermolysis bullosa affect specific components in this region, and demonstrate the uniqueness of these structures to external tissues. As a first attempt to describe the network of molecules involved in the interaction of epithelial cells with molecules deep in the underlying matrix, we have produced monoclonal antibodies to yet unrecognized components. Two of these antibodies have been selected for further characterization. One of them have immunological and biochemical characteristics similar to those expected for anchoring filaments. The other has characteristics resembling oxytalan fibers. We have shown that these antigens are synthesized by specific cell populations and have demonstrated the feasibility of their chemical characterization. We propose to isolate and characterize these antigens in detail, to identify the antigen with ultrastructurally observed fibrous components of the basement membrane zone, and to investigate potential interactions between these components and other known connective tissue elements. We anticipate that the proposed studies will provide specific information regarding these basement membrane zone proteins and will help form a basis for the understanding of the structure of this unique region. This information will provide the background for forming hypotheses regarding the molecular events underlying the pathogenesis of epidermolysis bullosa and bullous pemphigoid.