Differential expression of Ia molecules by human monocytes

Human immune response genes can be divided into three distinct loci, each of which codes for three distinct families of Ia molecules: HLA-SB, HLA-DC, and HLA-DR. The tissue distribtion and function of only one of these Ia molecules, HLA-DR, has been thoroughly studied. Using monoclonal antibodies, we examined the display of HLA-DR and HLA-DC molecules by adherent, human peripheral blood monocytes. The results of these studies demonstrate that although all human peripheral blood monocytes display easily detectable HLA-DR molecules, only 50% display easily detectable HLA-DC molecules. Separation of peripheral blood monocytes into HLA-DC⁺ and HLA-DC^- cells demonstrates that each population displays an equivalent density of HLA-DR molecules. Therefore, on the basis of differences in their display of these two Ia molecules, adherent peripheral blood monocytes can be divided into two broad populations: HLA-DR⁺, HLA-DC⁺, and HLA-DR⁺, HLA-DC^-. Despite the discoordinate display of these Ia antigens, the expression of both HLA-DR and HLA-DC can be regulated by a common signal, gamma interferon (IFN-γ). Incubation of monocytes for 96 h in autologous serum leads to a marked decrease in the expression of both HLA-DR and HLA-DC. Addition of recombinant IFN-γ to the cultures leads to reexpression of both HLA-DR and HLA-DC to levels comparable to those seen in fresh monocytes. In addition, although IFN-γ does not modulate all monocyte surface markers, it can be demonstrated to modulate expression of one marker, MAC 120, in a manner similar to that observed for Ia antigens. These studies demonstrate that among human peripheral blood monocytes, the distribution of the Ia molecule, HLA-DC, is not coordinate with that of HLA-DR, although both respond to the same regulatory signal.