caused by posttranscriptional events or failure to trans-The expression of the HLA class I molecules on the port and load peptides necessary for HLA expression. cell surface was investigated in hepatocellular carci-The selective loss of HLA-B and -C, but not -A, molecules noma (HCC) cell lines using complement-mediated cyto-(which also excludes a b 2 -microglobulin defect) is intoxicity (CMC) and flow cytometric analysis. Although triguing, and may be attributable to the ability of some HLA-A antigens were detected by CMC in all cell lines of the HLA-A molecules to load signal peptides not retested, HLA-B and -C antigens were not detectable in six quiring TAP transport, or to natural selection by HLA-B of seven HCC cell lines. These results were also conor -C locus-specific immune surveillance. (HEPATOLOGY firmed by flow cytometric analysis focusing on HLA-Bw4 1996;23:1181-1188.) and Bw6 public antigens. Furthermore, complementary DNA (cDNA) from each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated It is commonly accepted that the expression of HLA with antigen processing genes (TAP1 and TAP2). Two class I molecules on the cell surface is pivotal for the cell lines showed a reduced level of one or both of the recognition of tumor cells by cytotoxic T lymphocytes TAP messenger RNAs (mRNAs), and one of these showed a reduction of HLA-B and -C gene expression as well, (CTL), because CTL recognize the endogenously probut the others had detectable mRNA levels. These results cessed antigenic peptides in the association with HLA demonstrate that hepatocellular carcinoma cell lines molecules expressed on the cell surface. [1][2][3][4] In the case tested in the current study lose or decrease the expresof tumor cells, the endogenous peptide of interest is sion of HLA-B and -C alleles on the cell surface, even probably from a self protein that has incurred a mutathough mRNA encoding these alleles is present, sugtion or from an overexpressed wild-type protein. Extengesting that the loss of the HLA molecules might be sive efforts have been applied for eluting and identifying these tumor antigens, and some tumor-specific antigens that can be recognized by class I-restricted Abbreviations: CTL, cytotoxic T lymphocyte; HCC, hepatocellular carci-CTL have been identified and characterized. 5 The recnoma; CMC, complement-mediated cytotoxicity; IFN-g, interferon gamma; ognition of a tumor cell by CTL is regulated by the PCR, polymerase chain reaction; cDNA, complementary DNA; TAP, transinteraction between T-cell receptor and the ternary porter associated with antigen processing; ER, endoplasmic reticulum; FCS, fetal calf serum; MAb, monoclonal antibody; mRNA, messenger RNA; NK, complex of HLA, antigenic peptide, and b 2 -microglobunatural killer.