This research aims at an overall understanding of the way in which specialized cell types process and present antigen to initiate a variety of T-cell responses. We propose to study three major types of antigen presenting cells (ABC); dendritic cells, macrophages and B-cells. One hypothesis we wish to test is that dendritic cells may present small soluble antigens directly to T cells but that large and particulate antigens require preliminary digestion. A major point at issue is whether dendritic cells can perform these functions of whether other specialized cells (macrophages) are best equipped to deal with these antigens. Another major point to be tested is whether and how antigen epitopes associate with Ia antigens on the surface of APC for presentation to specific T cells. To answer these questions we intend using a unique system in which a variety of T cell responses can be elicited in Lewis rats, all specific for a simple determinant N-acetyl tyrosine azobenzenearsonate (ABA-tyr). This permits us to synthesize a variety of structures to which the ABA molecule can be attached enabling us to study such properties of an antigen as size, charge, digestibility etc. In the course of this work we expect to develop techniques for purifying and growing large quantities of the various APC's to enable biochemical work to be done. Antigen presentation represents perhaps the first and least understood step in the immune response. It's elucidation will provide a major tool for control enabling us to increase responsiveness where required (e.g. immunity to infection) or suppress it when necessary (e.g. autoimmune disease or graft rejection).
