A reevaluation of the putative association between the Fc gamma receptor and histocompatibility antigens on human mononuclear leukocytes.

The controversial question of an association between human Ia antigens and the FcR for immunoglobulin G has been examined. The experimental basis upon which such a relationship has been predicted was reevaluated. Human allosera with specificity for classical transplantation antigens, HLA-DR, and the related supertypic specificities MB and MT have been tested for their capacities to inhibit homologous EA rosette formation by PBM and B-CLL cells. Both immune and "nonimmune" sera inhibited rosette formation. Sera were normalized with respect to IgG concentration, and no significant quantitative differences in the observed inhibition were seen. Positive reactivity of the antisera with Ia, HLA-A, or HLA-B antigens did not influence EA binding to FcR. Furthermore, F(ab')2 of IgG from reactive sera did not inhibit rosette formation. These observations have been extended using murine reagents. A.TH anti-A.TL serum, which reacts with human Ia in binding and immunoprecipitation studies, and five monoclonal antibodies, which have been raised against human Ia and bind to monomorphic determinants, were tested for an effect on EA rosette formation. When these reagents were tested at concentrations at which they could be shown to bind to antigens on the target cell population, no inhibition of EA rosette formation by human PBM, MON or B-CLL cells could be demonstrated. The studies provide no evidence to suggest the existence of an association between Ia and the human FcR.