HLA CLASS-II EXPRESSION IN UNINDUCIBLE HEPATOCARCINOMA CELLS AFTER TRANSFECTION OF AIR-1 GENE-PRODUCT CIITA - ACQUISITION OF ANTIGEN-PROCESSING AND PRESENTATION CAPACITY

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 hepat ocarcinoma cell lines Alexander and HepG2 remains unmodified after tre atment with IFN-gamma, although MHC class I expression is up-modulated . This correlates with absence of CIITA mature transcripts. Transfecti on 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 ce ll lines, at the level of CIITA transcription and not at the level of IFN-gamma receptor binding and signal transduction mechanisms. To asse ss whether MHC class II expression on CIITA-transfected Alexander cell s 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 suppleme nted peptide but also process Ag85 protein to generate the specific ep itope recognized by the HLA-DR-restricted T cell line. Similar results were obtained with CIITA-transfected CFPAC-1 pancreatic adenocarcinom a cells, which differed from Alexander cells in that they were inducib le 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.