Tyrosine Phosphorylation Regulates the Expression of Major Histocompatibility Complex Antigens on a Human Lung Cancer Cell Line by Interferon-gamma

Expression of major histocompatibility complex (MHC) antigens on cancer cells is essential for cell-mediated immune function. However, these molecules are reduced on cancer cells enabling them to escape from host immune surveillance. It is well known that interferon-γ (IFN-γ) upregulates the expression of MHC molecules and restores the immunogenicity of cancer cells. Nevertheless, the mechanism by which IFN-γ modulates MHC expression on cancer cells is not clear. Therefore, in this report, we examined the role of tyrosine protein kinases in IFN-γ-induced MHC expression in a human lung adenocarcinoma cell line, HLC-1. We found that a tyrosine protein kinase inhibitor, herbimycin A, inhibited both IFN-γ-inducible MHC class I and class II expression, as assessed by flow cytometry. Additionally, assessment of tyrosine phosphorylation of cellular substrates by confocal laser microscopy using an anti-phosphotyrosine monoclonal antibody (mAb) revealed that IFN-γ induced protein tyrosine phosphorylation within 5 min of treatment. Herbimycin A inhibited this IFN-γ-induced tyrosine phosphorylation. Thus, tyrosine phosphorylation plays an important role in IFN-γ-induced MHC class I and class II expression on HLC-1 cells.