TRANSLATIONAL CONTROL OF MHC CLASS-II I-A MOLECULES BY IFN-GAMMA

MHC class II molecules are expressed in a limited number of cell types , including B lymphocytes and macrophages (M phi). IFN-gamma increases the surface expression of class II molecules in a murine B cell line without inducing detectable changes in either I-A or I-A mRNA levels. In bone marrow-derived M phi, IFN-gamma causes an increase in class II expression at both the mRNA and surface levels, In addition to the in crease in transcription rates described for M phi, IFN-gamma increases the rate of synthesis of IA alpha and IA beta proteins and the riboso me loading for both mRNA molecules in both cell types. Interestingly, there is a significant peak of free I-A mRNA in noninduced cells, Ther efore, IFN-gamma regulates the expression of MHC class II molecules at the translational level in both B cells and M phi and, as already rep orted, at the transcriptional level only in M phi. The actual mechanis m of regulation causes changes in the translation initiation rates in both cell types, as demonstrated by an increase in ribosome loading in polysome gradients.