Mechanisms of suppression of experimental autoimmune encephalomyelitis (EAE) by synthetic compounds and fusion antibodies
By: by Joel N.H. Stern
Published: 2008
Language: eng
Number of pages: 354
Description: This scientific work focuses on the study of autoimmunity in the murine model of Multiple Sclerosis (MS), namely experimental autoimmune encephalomyelitis (EAE). The primary objective of my investigation is the development of novel treatments for this autoimmune disease. Along with studying the basic mechanisms of their pathogenesis, I am exploring means by which one can regulate these diseases through designing and administering immune (system) modulators. Included among such modulators are two main categories of compounds: synthetic peptides and amino acid copolymers. These are modeled after the binding motif of auto-antigens to class II major histocompatibility complexes (MHC) molecules, with the purpose of disease suppression in mind. An alternative approach involves designing an in vivo auto- antigen delivery system using monoclonal fusion antibodies coupled with MS auto-antigens. The system targets the antigen uptake through multilectin receptor DEC-205 on antigen presenting cells such as dendritic cells (DC). Following DEC-205 mediated binding, antigens are processed onto MHC molecules and presented. The mechanism by which these fusion antibodies alter immune responses is currently under investigation. Our preliminary results suggest, however, that at low dosages they may somehow convert pathogenic T cells into iv regulatory T cells and/or delete pathogenic T cells. This method of antigen delivery may be more efficient in modulating T cell activation than peptides delivered in solution. My studies demonstrated that lectin receptor mediated peptide delivery to DC and copolymer induced tolerance are mechanisms that independently regulate auto-reactive T cell responses and may provide the basis of a new therapeutic approach in the treatment of autoimmune diseases. Our major goal is to bring one of our compounds to clinical trials in order to treat MS patients.
Notes: "September 2008."

Thesis (Ph.D., Dept. of Biological Sciences in Dental Medicine)--Harvard University, 2008.

Includes bibliographical references.