Markedly decreased expression of TAP1 and LMP2 genes in HLA class I-deficient human tumor cell lines

Immunol Lett. 1996 May;50(3):149-54. doi: 10.1016/0165-2478(96)02531-x.

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 alpha chain, beta 2-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 basophilic leukaemia. These cell lines were deficient in expression of both class I alpha chain and beta 2-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 gamma-IFN markedly enhanced the expression of class I alpha chain, beta 2-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 gamma-IFN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics*
  • Cysteine Endopeptidases*
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Multienzyme Complexes*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Proteasome Endopeptidase Complex
  • Proteins / genetics*
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Histocompatibility Antigens Class I
  • Multienzyme Complexes
  • Proteins
  • TAP1 protein, human
  • beta 2-Microglobulin
  • LMP-2 protein
  • TAP2 protein, human
  • Cysteine Endopeptidases
  • LMP7 protein
  • Proteasome Endopeptidase Complex