The major goal of this proposal is to increase our understanding of the molecular basis of macrophage function in three facets of the immune response: 1) the activation of T helper cells. We plan to isolate and characterize variant progeny of an antigen presenting murine macrophage line that have structural alterations in the I-E molecule. Variants will be analyzed at the protein and the DNA level. These studies should help elucidate structure-function relationships in Ia molecules. 2) the induction of T suppressor cells. We are interested in identifying and characterizing the membrane antigen on murine macrophages that interacts wit I-J bearing T lymphocytes. Macrophage lines will be generated that bear this molecule. 3) the interaction with antigen antibody complexes. The interaction of the immunoglobulin with murine macrophage Fc receptors will be further analyzed and the requirements for binding of immunoglobulin and for triggering of phagocytosis determined. The specificity of these receptors will be compared to those on B and T lymphocytes. For these studies mutant myeloma proteins and cleavage fragments of myeloma proteins will be used. In addition we will use monocyte cell lines generated from peripheral blood monocytes of normal individuals and patients with SLE to study Fc receptor function on human monocytes. We will also try to use human monocyte lines as accessory cells in antigen presentation assays and isolate mutants in human Class II histocompatibility antigens.
