Low‐molecular‐weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line

Abstract

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 BEL7,404. Expression of HLA-I and antigen presentation-related genes were analyzed by flow cytometry and polymerase chain reaction. The HLA class I-deficient BEL7,404 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. The BEL7,404 cells downregulated the expression of HLA class I antigen and lacked expression of LMP2 and LMP7. Interferon (IFN)-gamma treatment increased the expression of LMP2 but not LMP7. The LMP2-transfected BEL7,404 cells or LMP2 and LMP7-cotransfected cells restored surface HLA class I expression while LMP7-transfected cells did not. However, in IFN-gamma-treated BEL7,404 cells, transfection with the LMP7 gene induced more HLA class I expression than mock transfection. The LMP2 gene was required for the expression of HLA class I molecules in BEL7,404. The LMP7 was not the major reason for loss of HLA class I in BEL7,404 cells, although the supply of exogenous LMP7 could increase surface expression of HLA class I antigen.