Low-molecular-weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line
Article first published online: 5 JUL 2006
Journal of Gastroenterology and Hepatology
Volume 22, Issue 7, pages 1155–1161, July 2007
How to Cite
Shen, Y.-Q., Zhang, J.-Q., Xia, M., Miao, F.-Q., Shan, X.-N. and Xie, W. (2007), Low-molecular-weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line. Journal of Gastroenterology and Hepatology, 22: 1155–1161. doi: 10.1111/j.1440-1746.2006.04421.x
- Issue published online: 5 JUL 2006
- Article first published online: 5 JUL 2006
- Accepted for publication 11 December 2005.
- antigen presentation;
- hepatocellular carcinoma;
- human leukocyte antigens;
Background: Tumor cells may alter the expression of numerous components involved in antigen-processing machinery to decrease human leukocyte antigen (HLA) class I expression, allowing the tumor cells to escape immune surveillance. The purpose of the present study was to investigate the involvement of these components in the downregulation of HLA class I expression in human hepatocellular carcinoma cell line BEL7404.
Methods: Expression of HLA-I and antigen presentation-related genes were analyzed by flow cytometry and polymerase chain reaction. The HLA class I-deficient BEL7404 cell was transfected with the low-molecular-weight protein (LMP) 2 and LMP7 gene and were analyzed by flow cytometry for restoration of surface HLA class I expression.
Results: The BEL7404 cells downregulated the expression of HLA class I antigen and lacked expression of LMP2 and LMP7. Interferon (IFN)-γ treatment increased the expression of LMP2 but not LMP7. The LMP2-transfected BEL7404 cells or LMP2 and LMP7-cotransfected cells restored surface HLA class I expression while LMP7-transfected cells did not. However, in IFN-γ-treated BEL7404 cells, transfection with the LMP7 gene induced more HLA class I expression than mock transfection.
Conclusions: The LMP2 gene was required for the expression of HLA class I molecules in BEL7404. The LMP7 was not the major reason for loss of HLA class I in BEL7404 cells, although the supply of exogenous LMP7 could increase surface expression of HLA class I antigen.