The overall goal of these studies is to explore the interactions of the human immune system with specific group A streptococcal antigens as these may play a role in the development of rheumatic fever (RF) and rheumatic heart disease (RHD). The specific aims are to characterize the mechanism and dynamics of the altered proliferative response to streptococcal antigens of peripheral blood and tonsillar lymphocytes from RHD patients and to compare these with those of non-RHD patients. The humoral immune response to streptococcal antigens will be examined and we will define the cell surface characteristics and functional properties of cell species involved in the altered immune response in RHD. In addition we propose to study family patterns of response to streptococcal antigens and the presence of unique cell surface structures associated with RF/RHD as defined by monoclonal antibodies against B cell alloantigens. These studies should define a possible inherited susceptibility to RF/RHD and should allow the identification of those individuals with the potential for the development of these diseases.