The proposed research will define: (a) structure-function interrelationships of two closely associated, independent immunodeterminants within the rat-specific encephalitogenic region of myelin basic protein (MBP) which specify EAE induction/transfer of the disease with primed, activated lymphoid cells and in vitro proliferative responses of primed lymphyoid cells, respectively, (b) the role of the clotting system and fibrinolysis in particular in regulating permeability of the blood-brain barrier which temporally coincides with appearance of clinical manifestations of EAE in rats and subsequent clinical remission-return of well being, and (c) prerequisite cellular and humoral factors for MBP-stimulated in vitro proliferative responses and activated cell transfer of EAE using peripheral blood leukocytes of MBP-sensitized rats. The anticipated results of this research will: (a) provide molecular insight into the amino acid sequences comprising the immunodeterminants of MBP responsible for EAE in rats and the specific interactions of these immunodeterminants with each other and with the lymphoid cells causing the disease, (b) add additional evidence for participation of the coagulation cascade in relationship to the critical role of BBB permeability in the immunopathogenesis of EAE in rats, and (c) allow MBP-reactive lymphocytes in the vascular compartment to be incorporated into EAE research in rats. New knowledge of EAE from this research should prove applicable to analogous neuroimmunologic disorders of human beings, e.g., multiple sclerosis.
