Although a great deal is known about the sub-populations of lymphocytes which are involved in the immune response, far less is known about the """"""""accessory"""""""" cells which present antigen to activate the various lymphocytes.
The aim of these proposed studies is to identify and characterize antigen presenting cells which will be isolated from mouse spleen. A central hypothesis to be tested is that there are unique sets of antigen presenting cells for specific subsets of functional lymphocytes. The studies will focus on the function and mechanism of action of the splenic dendritic cell which we have shown to present soluble protein antigens to antigen-specific syngeneic T cells. The properties of the dendritic cell will be compared both functionally and biochemically with macrophage populations. Using antigen-specific T cell hybridomas, we will enquire as to whether dendritic cells can present large particulate antigens as well as small soluble proteins to helper T cells. A major interest will be to test if the non-phagocytic dendritic cell by itself is able to present these different forms of antigen or alternatively whether the degradative capacity of a macrophage is also required for at least some antigens. Possible mechanisms of co-operation between accessory cells will also be tested. Studies on the ability of dendritic cells and macrophages to activate other sets of T cells such as T suppressor and contrasuppressors will also be performed. The genetic restriction on the interaction between the presenting cells and different T cell subsets will be assessed by using anti-I-A, I-J and H-2D antibodies. Lines of transformed dendritic cells will be developed and attempts will be made to isolate precursor cells from bone marrow. These studies will help to elucidate the nature of the heterogeneity of antigen presenting cells and moreover may yield important information on mechanisms by which the triggering of T subsets may be potentially manipulated in disease states.
