EXPRESSION OF HLA CLASS-I MOLECULES AND THE TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING IN HEPATOCELLULAR-CARCINOMA

The expression of the HLA class I molecules on the cell surface was in vestigated in hepatocellular carcinoma (HCC) cell lines using compleme nt-mediated cytotoxicity (CMC) and flow cytometric analysis, Although HLA-A antigens were detected by CMC in all cell Lines tested, HLA-B an d-C antigens were not detectable in six of seven HCC cell lines. These results were also confirmed by now cytometric analysis focusing on HL A-Bw4 and Bw6 public antigens, Furthermore, complementary DNA (cDNA) h om each cell line was tested for the expression of HLA-A, -B, -C and t he transporter associated with antigen processing genes (TAP1 and TAP2 ). Two cell lines showed a reduced level of one or both of the TAP mes senger RNAs (mRNAs), and one of these showed a reduction of HLA-B and -C gene expression as well, but the others had detectable mRNA levels. These results demonstrate that hepatocellular carcinoma cell lines te sted in the current study lose or decrease the expression of HLA-B and -C alleles on the cell surface, even though mRNA encoding these allel es is present, suggesting that the loss of the HLA molecules might be caused by posttranscriptional events or failure to transport and load peptides necessary for HLA expression, The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta(2)-microglobuli n defect) is intriguing, and may be attributable to the ability of som e of the HLA-A molecules to load signal peptides not requiring TAP tra nsport, or to natural selection by HLA-B or -C locus-specific immune s urveillance.