Relationship of macrophage Ia and membrane IL 1 expression to antigen presentation

Membrane expression of Ia molecules by antigen-presenting cells is critical for the induction of T cell responses to foreign protein antigens (reviewed in Reference 1). In addition, antigen-specific T cell proliferation has been thought to be dependent on interleukin 1 (IL 1) secretion by antigen-presenting cells. Recently, we have described a novel membrane-bound form of IL 1 that is required for the presentation of antigen by antigen-pulsed, fixed macrophages. Membrane IL 1 is a mitogenic protein found on the macrophage membrane that, like soluble IL 1, stimulates thymocytes and IL 1-dependent T cells but not IL 1-dependent T cell lines. This activity is inhibited by a polyclonal anti-IL 1 antibody. Membrane IL 1 is an integral membrane protein and does not represent soluble IL 1 nonspecifically bound or fixed to the macrophage membrane. Additional biochemical studies are required to define the possible interrelationships between soluble and membrane IL 1. We have now developed a method for independently varying the levels of Ia and membrane IL 1 expression on macrophages in culture. By then fixing the cells, we are able to preserve constant levels of these molecules during the assay for antigen presentation. Using this system, we have demonstrated that quantitative variation in these two parameters was associated with changes in the magnitude of the T cell response.