Introduction of tapasin gene restores surface expression of HLA class I molecules, but not antigen presentation of an HIV envelope peptide in a hepatoma cell line.
A hepatoma cell line, Hep G2, reveals the diminished HLA class I surface expression and the reduced expression of LMP2, LMP7, and tapasin transcripts, suggesting that the reduced expression of these transcripts may be associated with the low expression of HLA class I molecules. Introduction of tapasin gene dramatically up-regulates the surface expression of HLA class I molecules on Hep G2 cells, and unexpectedly, enhances the expression of LMP2 and LMP7 transcripts as well. Unlike Hep G2, these tapasin-transfected Hep G2 cells are recognized by allo-specific CTL. However, the transfectant is unable to endogenously present an HIV envelope peptide to an HIV-specific CTL clone, suggesting that a proteasome-independent antigen processing pathway exists and still remains defective in the transfectant. These data may provide significant evidence that the nonproteasomal antigen processing pathway as well as the proteasomal pathway may be impaired in tumor cells to escape immune surveillance performed by CTL.
Matsui
M
M
Department of Microbiology, Saitama Medical School, Moroyama-Cho, Iruma-Gun, Saitama 350-0495, Japan.
Machida
S
S
Tomiyama
H
H
Takiguchi
M
M
Akatsuka
T
T
D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D003546:Cysteine Endopeptidases; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D015686:Gene Products, env / Q000235:genetics*; D005805:Genes, MHC Class I; D015752:Genes, env; D015497:HIV-1 / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D007157:Immunologic Surveillance; D008113:Liver Neoplasms; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics
D017920:Antiporters; D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015686:Gene Products, env; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D014763:Viral Matrix Proteins; C107762:tapasin; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex