During the next year it is planned to extend our previous work on the molecular and cellular mechanisms involved in the activation of T and B cells through their Fc receptors. Experiments will be carried out to determine if the 14,000 molecular weight subfragment generated from Fc fragments by macrophage has affinity for T cells, B cells or macrophages. Other studies will be designed to better understand the structure of the 14,000 m.w. subfragment that is involved in both the proliferative and polyclonal response. Experiments are designed to determine if the 14,000 m.w. subfragment is a single polypeptide chain or a dimer. Preliminary data suggest that the active subfragment is located in the CH3 domain of immunoglobulin. Other studies will be carried out to further clarify the characteristics of the macrophage involved in activation of lymphocytes by Fc fragments; i.e., are the effective macrophages Ia-positive or Ia-negative. Considerable effort will be devoted to characterization of TRF generated by the Fc fragments as to both its biological and physicochemical properties. Attempts will also be made to identify soluble factors that are generated from T cells by Fc fragments that are responsible for the adjuvant effect of these fragments. Additional studies will be carried out to further characterize the cellular events involved in the activation of T and B cells by soluble antigen-antibody complexes. A comparison of these latter cellular events with those involved in the activation of lymphocytes by Fc fragment will be compared. If such active soluble factors can be identified, experiments will be designed to see if these soluble factors are also responsible for the enhancement and regulation of cell-mediated responses, such as the mixed lymphocyte reaction and T cell cytotoxicity.