T cell autoreactivity against a 28 kD biliary protein (B1-p28) in primary biliary cirrhosis

Cellular immune responses against biliary epithelial cells are important in understanding the pathogenesis of primary biliary cirrhosis. We previously reported a biliary antigen B1 which stimulated peripheral T lymphocytes of primary biliary cirrhosis as a possible, non-mitochondrial target of biliary epithelial cells. Further characterization of B1 was performed.

To confirm localization of B1 in biliary epithelial cells, a mouse monoclonal antibody was raised against B1. As B1 could be separated into two main components by SDS-PAGE under reducing condition, these components were individually cut out from Western blots and converted into antigen-bearing particles for a proliferation assay to detect the antigenic component responsible for stimulating lymphocytes. The relation of this proliferation to HLA DR antigens was also analyzed.

Immunohistochemically, B1 was shown to be specifically expressed on biliary epithelial cells of human liver tissue. Of two components from B1 under reducing condition, prominent proliferation against B1-p28, a 28 kD component of B1 was detected in primary biliary cirrhosis. The reactivities were significantly higher than chronic liver diseases (p < 0.001) or normal controls (p < 0.001). Furthermore, high responders to B1-p28 were observed frequently in primary biliary cirrhosis patients with HLA DR8 (p < 0.02), which was susceptible to the development of primary biliary cirrhosis.

These data suggest B1-p28 expressed on biliary epithelial cells is a candidate for the target antigen of primary biliary cirrhosis in addition to mitochondrial autoantigens. Further characterization of B1-p28 may provide new insight into the autoimmune mechanisms of primary biliary cirrhosis.