ELSEVIER Immunology Letters 50 (1996) 149- 154 Markedly decreased expression of TAP1 and LMP2 genes in HLA class I-deficient human tumor cell lines Dharam P. Singal *, Ming Ye, Jin Ni, Denis P. Snider zyxwvutsrqponmlkjihgfedcbaZYXWV Department of Pathoiogy, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canaa’a L8N _TZzS Received 4 January 1996; accepted 8 March 1996 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP Abstract HLA class I antigens of the human major histocompatibility complex play an important role in immune response. These molecules present foreign antigenic peptides to cytotoxic T lymphocytes and thereby play a role in the immune surveillance of cells infected with virus or other intracellular pathogens or altered by malignant transformation. A marked deficiency or lack of expression of these antigens has been reported in a variety of human neoplasms. In the present study, we examined the expression of class I a chain, P,-microglobulin, TAP (TAP1 and TAP2) and LMP (LMP2 and LMP7) genes in a number of human tumor cell lines including small-cell lung carcinoma, hepatocellular carcinoma, colon adenocarcinoma and bdsophilic leukaemia. These cell lines were deficient in expression of both class I CIchain and /Y,-microglobulin gene products. In addition, these cell lines lacked the products of MHC-encoded proteasome subunit LMP2 as well as the putative peptide transporter TAP1 genes. In contrast, TAP2 and LMP7 genes were expressed in these cell lines. Treatment of cells with y-IFN markedly enhanced the expression of class I c( chain, a,-microglobulin, TAP1 and LMP2 genes with a concomitant increase in cell-surface expression of class I molecules. The upregulation of TAP1 and LMP2 expression is associated with increased class I expression, suggesting that endogenous antigens, e.g. tumor antigens, could be presented by class I molecules following treatment of tumor cells with >I-IFN. Keywords: TAP; LMP genes; Tumor cell lines; HLA antigens 1. Introduction HLA class I molecules are transmembrane glyco- proteins composed of a highly polymorphic heavy (class I g) chain, encoded by genes of three different (A, B and C) loci on the short arm of chromosome 6, and a light chain (/&microglobulin) encoded by a gene on chromosome 15. These HLA-A, B, C molecules func- tion as recognition structures in immune response be- cause they present foreign antigenic peptides to cytotoxic T lymphocytes, with different HLA alleles varying in their abilities to present different antigen epitopes [ 1,2]. HLA class I molecules therefore play an important role in immune surveillance of cells infected with virus or other intracellular pathogens or altered by malignant transformation [3]. A decreased or lack of expression of HLA-A, B, C antigens on malignant cells will affect host’s immune response and thus has impli- *Corresponding author. Tel.: + 1 905 525-9140, ext. 22473: fax: + 1 905 522 6750. cations in tumor growth and metastasis [4]. HLA class I antigens are expressed on most nucle- ated cells and platelets. However, a marked deficiency or lack of expression of these antigens has been ob- served in a variety of human neoplasms, including small-cell lung carcinoma, cervical carcinoma, hepato- cellular carcinoma, colon carcinoma. embryonal car- cinoma, and B cell lymphoma [5-131. In addition, a relationship between loss of class I expression and histopathologic changes in malignancy has been re- ported [13,14]. Furthermore, in mice and rats, restora- tion of class I expression by transfection of syngeneic genes led to tumor rejection and/or abrogation of metastasis formation [ 15- 171. Down regulation of cell-surface expression of HLA class I molecules has generally been attributed to low levels of heavy (class I a) chain or light (/?,-microglobu- lin) chain gene transcription [5,18,19]. The transfection of class I OL chain and the use of DNA-hypomethylating or alkylating agents, however, did not always result in enhanced class I expression in tumors [20,21]. In this 016%2478/96/$12.00 0 1996 Elsevier Science B.V. All rights reserved PII zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA SO 165-2478(96)0253 1-X