IMMUNOGLOBULIN ACCESS TO NEOANTIGENS ON CNS CELLS

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The circumstances under which antigen specific immunoglobulins of defined isotype can enter the central nervous system (CNS) and whether these immunoglobulins can overcome potential restrictions to their diffusion along interstitial pathways to reach and interact with antigens expressed on the surfaces of neural cells are essentially unknown. Despite this, CNS entry of immunoglobulins and their interaction with neural cells bearing neoantigens is critical to several current theories of the pathogenesis of autoimmune disorders of the CNS including multiple sclerosis and for the potential immunotherapy of a variety of CNS disorders. This study will utilize both autoradiographic and immunohistochemical morphologic approaches, and bulk transfer studies to determine whether, how and when defined monoclonal antibodies gain entry to the CNS in response to the appearance of neoantigens at the surfaces of brain cells. A recently developed library of monoclonal antibodies to the glycoproteins of mumps virus, immunocytochemical and autoradiographic approaches and the well described model of mumps-meningoencephalitis in hamsters combine to form the experimental system with which these problems will be approached.