Modulation of LFA-1 surface antigen expression by activated H-ras oncogene in EBV-infected human B-lymphoblast cells.

The lymphocyte-associated antigen 1 (LFA-1) involved in a wide range of cellular adhesion-dependent immunological functions, including interaction of cytotoxic T lymphocytes with their target, is implicated in tumorigenesis. The modulation of the LFA-1 antigen expression was studied in Epstein-Barr virus (EBV)-immortalized human B-lymphoblastoid cell lines, transfected with human oncogenes, H-ras and c-myc. We observed by flow cytometry that the activated H-ras (EJ) gene, but not its normal counterpart, consistently enhanced LFA-1 expression. The RNA analysis revealed that induction of the LFA-1 surface antigen by the EJ gene occurred through the level of the alpha-chain but not the beta-chain mRNA of LFA-1. The LFA-1 molecules induced by the EJ gene were functional; cells with the EJ gene revealed an elevated level of homocytic cellular adhesion, which was blocked by the anti-LFA-1 monoclonal antibody. Flow cytometry analysis indicated that the modulation of the LFA-1 antigen expression was a phenomenon specific to the EJ gene. The high levels of expression of c-myc and blc-2 gene did not affect LFA-1 antigen expression. The system used here provides a tool by which the signal transduction pathway involving the H-ras gene and the molecular mechanism of LFA-1 gene expression can be genetically dissected.