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We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24,000 and 60,000. Further differences were observed with respect to the species specificity and (among the non-organ-specific antibodies) pattern of tissue cross-reactivity. Our results demonstrate the presence of several liver-specific determinants and membrane components within LSP. There are, however, a very much greater number of non-organ-specific epitopes and numerous determinants displayed on intracellular structures. This emphasizes the remarkable heterogeneity of the antigen preparation named LSP and warrants the use of clearly defined antigens in further studies dealing with auto-immune phenomena in liver diseases.
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