MARKEDLY DECREASED EXPRESSION OF TAP1 AND LMP2 GENES IN HLA CLASS I-DEFICIENT HUMAN TUMOR-CELL LINES

HLA class I antigens of the human major histocompatibility complex pla y an important role in immune response. These molecules present foreig n antigenic peptides to cytotoxic T lymphocytes and thereby play a rol e in the immune surveillance of cells infected with virus or other int racellular pathogens or altered by malignant transformation. A marked deficiency or lack of expression of these antigens has been reported i n a variety of human neoplasms. In the present study, we examined the expression of class I alpha chain, beta(2)-microglobulin, TAP (TAP1 an d TAP2) and LMP (LMP2 and LMP7) genes in a number of human tumor cell lines including small-cell lung carcinoma, hepatocellular carcinoma, c olon adenocarcinoma and basophilic leukaemia. These cell lines were de ficient in expression of both class I alpha chain and beta(2)-microglo bulin gene products. In addition, these cell lines lacked the products of MHC-encoded proteasome subunit LMP2 as well as the putative peptid e transporter TAP1 genes. In contrast, TAP2 and LMP7 genes were expres sed in these cell lines. Treatment of cells with gamma-IFN markedly en hanced the expression of class I alpha chain, beta(2)-microglobulin, T AP1 and LMP2 genes with a concomitant increase in cell-surface express ion of class I molecules. The upregulation of TAP1 and LMP2 expression is associated with increased class I expression, suggesting that endo genous antigens, e.g. tumor antigens, could be presented by class I mo lecules following treatment of tumor cells with gamma-IFN.