Molecular and functional phenotypes of melanoma cells with abnormalities in HLA class I antigen expression

Tissue Antigens. 1996 May;47(5):382-90. doi: 10.1111/j.1399-0039.1996.tb02573.x.

Abstract

Analysis of melanoma cell lines with abnormalities in HLA Class I antigen expression has identified two serological phenotypes caused by distinct molecular defects. One is characterized by lack of HLA Class I antigen expression which is not induced by IFN-gamma or by incubation at 25 degrees C for 24 hrs. This phenotype reflects structural changes in the beta(2)m gene which interfere with its transcription and/or translation or result in the synthesis of a defective beta(2)-mu polypeptide unable to associate with HLA Class I heavy chains. The other phenotype manifests very low HLA Class I antigen expression which is enhanced by IFN-gamma or by incubation at 25 degrees C for 24 hrs. This phenotype reflects abnormalities in TAP heterodimer expression, which cause defects in stable assembly and intracellular transport of the HLA Class I antigen trimolecular complex. Loss of HLA Class I antigens renders melanoma cells resistant to lysis by HLA Class I antigen-restricted cytotoxic T cells which specifically recognize melanoma associated antigens. Therefore, abnormalities in HLA Class I antigen expression may have a negative impact on the outcome of T cell based immunotherapy. Characterization of the molecular defects underlying loss of HLA Class I antigens may suggest approaches to restore their expression. Inclusion of these approaches in the protocols of T cell based immunotherapy may improve its efficacy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / immunology
  • Amino Acid Transport Systems*
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • DNA, Complementary / genetics
  • Exoribonucleases*
  • Fungal Proteins / immunology
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Genes, MHC Class I*
  • HLA Antigens / biosynthesis
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive
  • Interferon-gamma / pharmacology
  • Interleukin-12 / pharmacology
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / genetics
  • Melanoma / immunology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Saccharomyces cerevisiae Proteins
  • T-Lymphocytes, Cytotoxic / immunology
  • Trans-Activators / immunology
  • beta 2-Microglobulin / biosynthesis
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Amino Acid Transport Systems
  • Antigens, Neoplasm
  • DNA, Complementary
  • Fungal Proteins
  • HLA Antigens
  • Interleukin-2
  • Neoplasm Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • TAT2 protein, S cerevisiae
  • Trans-Activators
  • beta 2-Microglobulin
  • TAP2 protein, human
  • Interleukin-12
  • Interferon-gamma
  • Exoribonucleases