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

Abstract

BACKGROUND/AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: T Miyamoto, T Maeda, S Onishi, Y Yamamoto
• Journal: Journal of hepatology (J Hepatol) Vol. 22 Issue 4 Pg. 423-30 (Apr 1995) ISSN: 0168-8278 [Print] Netherlands
• PMID: 7545198 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• B1-p28 protein, human
• Epitopes
• HLA-DR Antigens
• HLA-DR Serological Subtypes
• HLA-DR8 antigen
• Proteins

Topics

• Aged
• Antibodies, Monoclonal
• Autoimmunity
• Bile (metabolism)
• Electrophoresis, Polyacrylamide Gel
• Epitopes
• Female
• HLA-DR Antigens (immunology)
• HLA-DR Serological Subtypes
• Humans
• Immunohistochemistry
• Liver Cirrhosis, Biliary (immunology)
• Lymphocyte Activation
• Male
• Middle Aged
• Proteins (immunology)
• T-Lymphocytes (immunology)