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HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA: acquisition of antigen processing and presentation capacity.
J Immunol. 1998 Jul 15; 161(2):814-20.JI

Abstract

The AIR-1-encoded CIITA transcriptional activator is crucial for both constitutive and IFN-gamma-induced MHC class II gene transcription. We show here that the MHC class II negative phenotype of the human hepatocarcinoma cell lines Alexander and HepG2 remains unmodified after treatment with IFN-gamma, although MHC class I expression is up-modulated. This correlates with absence of CIITA mature transcripts. Transfection of an expressible CIITA cDNA in Alexander cells resulted in a very high cell surface expression of all three human class II subsets, HLA-DR, -DP and -DQ, indicating that normally observed induction of CIITA expression by IFN-gamma is probably blocked, in the hepatocarcinoma cell lines, at the level of CIITA transcription and not at the level of IFN-gamma receptor binding and signal transduction mechanisms. To assess whether MHC class II expression on CIITA-transfected Alexander cells could have functional relevance, we tested their capacity to present antigenic peptides to an HLA-DR-restricted T cell line specific for a peptide of Mycobacterium tuberculosis Ag85 protein. It was found that the transfected cells could not only present the exogenously supplemented peptide but also process Ag85 protein to generate the specific epitope recognized by the HLA-DR-restricted T cell line. Similar results were obtained with CIITA-transfected CFPAC-1 pancreatic adenocarcinoma cells, which differed from Alexander cells in that they were inducible by IFN-gamma. These results suggest new strategies to act on CIITA for increasing the potential of a tumor cell to present putative tumor Ags to the immune system.

Authors+Show Affiliations

Institute of Immunology and Infectious Diseases, University of Verona, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9670958

Citation

Sartoris, S, et al. "HLA Class II Expression in Uninducible Hepatocarcinoma Cells After Transfection of AIR-1 Gene Product CIITA: Acquisition of Antigen Processing and Presentation Capacity." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 2, 1998, pp. 814-20.
Sartoris S, Valle MT, Barbaro AL, et al. HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA: acquisition of antigen processing and presentation capacity. J Immunol. 1998;161(2):814-20.
Sartoris, S., Valle, M. T., Barbaro, A. L., Tosi, G., Cestari, T., D'Agostino, A., Megiovanni, A. M., Manca, F., & Accolla, R. S. (1998). HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA: acquisition of antigen processing and presentation capacity. Journal of Immunology (Baltimore, Md. : 1950), 161(2), 814-20.
Sartoris S, et al. HLA Class II Expression in Uninducible Hepatocarcinoma Cells After Transfection of AIR-1 Gene Product CIITA: Acquisition of Antigen Processing and Presentation Capacity. J Immunol. 1998 Jul 15;161(2):814-20. PubMed PMID: 9670958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA: acquisition of antigen processing and presentation capacity. AU - Sartoris,S, AU - Valle,M T, AU - Barbaro,A L, AU - Tosi,G, AU - Cestari,T, AU - D'Agostino,A, AU - Megiovanni,A M, AU - Manca,F, AU - Accolla,R S, PY - 1998/7/22/pubmed PY - 1998/7/22/medline PY - 1998/7/22/entrez SP - 814 EP - 20 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 161 IS - 2 N2 - The AIR-1-encoded CIITA transcriptional activator is crucial for both constitutive and IFN-gamma-induced MHC class II gene transcription. We show here that the MHC class II negative phenotype of the human hepatocarcinoma cell lines Alexander and HepG2 remains unmodified after treatment with IFN-gamma, although MHC class I expression is up-modulated. This correlates with absence of CIITA mature transcripts. Transfection of an expressible CIITA cDNA in Alexander cells resulted in a very high cell surface expression of all three human class II subsets, HLA-DR, -DP and -DQ, indicating that normally observed induction of CIITA expression by IFN-gamma is probably blocked, in the hepatocarcinoma cell lines, at the level of CIITA transcription and not at the level of IFN-gamma receptor binding and signal transduction mechanisms. To assess whether MHC class II expression on CIITA-transfected Alexander cells could have functional relevance, we tested their capacity to present antigenic peptides to an HLA-DR-restricted T cell line specific for a peptide of Mycobacterium tuberculosis Ag85 protein. It was found that the transfected cells could not only present the exogenously supplemented peptide but also process Ag85 protein to generate the specific epitope recognized by the HLA-DR-restricted T cell line. Similar results were obtained with CIITA-transfected CFPAC-1 pancreatic adenocarcinoma cells, which differed from Alexander cells in that they were inducible by IFN-gamma. These results suggest new strategies to act on CIITA for increasing the potential of a tumor cell to present putative tumor Ags to the immune system. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9670958/HLA_class_II_expression_in_uninducible_hepatocarcinoma_cells_after_transfection_of_AIR_1_gene_product_CIITA:_acquisition_of_antigen_processing_and_presentation_capacity_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9670958 DB - PRIME DP - Unbound Medicine ER -