The central thrust of this program is the study of the etiologic and pathogenetic factors involved in immunopathologic responses directed toward endogenous antigens. Among the endogenous antigens are included traditional autoantigens, viruses and tumor antigens since operationally the etiologic factors and pathogenic consequences of immune responses to each appear quite similar. Experiments are designed to investigate: 1) the control mechanisms which normally establish and maintain self tolerance, 2) the ways in which such controls may fail or be circumvented thereby permitting autoimmune responses, 3) the interaction of the immunologic effectors, antibodies and sensitized cells with endogenous or auto-antigens and 4) the pathogenic processes set in motion by the immunologic reactions. Specifically we will 1) analyze the behavior of lymphocyte surface glycoproteins during activation and cell-cell interactions as a means of studying regulatory processes, 2) investigate the processes of tolerance induction and termination and autoimmunity which may be associated with the latter, 3) make a comprehensive study of murine SLE concentrating on genetic and other etiologic factors and the critical pathogenetic processes leading to disease, 4) investigate the immunologic and nonimmunologic host factors which may influence the pathologic impact of immune complexes and 5) study mechanisms which permit viruses to remain latent and the effects of viral infection on the function of the immune system.
