IMMUNOMODULATION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY ANTIBODIES TO THE ANTIGEN-IA COMPLEX

AUTOIMMUNE diseases occur when T lymphocytes become activated on recognizing self antigen linked to the autologous class II molecule of the major histocompatibility complex (MHC) 1,2. The resulting complex of antigen MHC T-cell receptor could be a target for treatment of autoimmune diseases. Studies in which each component is blocked separately 3-10 might be limited by interference in non-relevant immune responses that either use the same set of T-cell-receptor V gene segments or are linked to the same MHC. We report here an attack by a specific antibody on the unique antigenic site formed by the binding of two components of the trimolecular complex, the autoantigen bound to the self MHC 11-14. We tested its effect in experimental allergic encephalomyelitis, an acute neurological autoimmune disease which is widely regarded as a model for autoimmune disorders 15-17 and which is mediated by CD4+ T cells recognizing myelin basic protein (BP), or its peptides, in association with self Ia 18,19. We made monoclonal antibodies which bound only the complex of BP and I-A(s). These antibodies blocked the proliferative response in vitro to the encephalitogenic determinant of BP and reduced the response to intact BP, without affecting the response to a nonrelevant antigen-purified protein derivative of tuberculin presented on syngeneic macrophages. They also inhibited experimental allergic encephalomyelitis in H-2s mice. Hence, antibodies directed specifically to the autoantigen-Ia complex, may offer a highly selective and effective treatment in autoimmune diseases.