Low-molecular-weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line.
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 BEL7,404.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Shen
Yu-Qing
YQ
State Education Ministry Laboratory of Developmental Genes and Human Diseases, Jiangsu Provincial Key Laboratory of Gene Diagnosis and Therapy, Genetics Research Center, Southeast University Medical School, Nanjing, Jiangsu Province, China.
Zhang
Jian-Qiong
JQ
Xia
Mei
M
Miao
Feng-Qing
FQ
Shan
Xiang-Nian
XN
Xie
Wei
W
D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D009097:Multienzyme Complexes / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex