Study of Antigen Presentation and Antigen-Specific Immunomodulation in Multiple Sclerosis by T cell Receptor-mimic Antibodies
During autoimmune diseases, like Multiple Sclerosis (MS), the immune system is downregulated in a non-specific manner in order to reduce inflammation. Consequently, targeting and specifically inhibiting autoreactive T cells is highly desirable as a treatment for autoimmune disease. We hypothesize that during the inflammatory process in MS, APCs can present several myelin derived epitopes simultaneously and consequently activate a variety of autoreactive T cells. Accordingly, targeting one of these epitopes with T cell receptor- mimic (TCRm) antibody (Ab) could result in the elimination of specific APCs, thus prevent epitope spreading, decrease myelin-specific T cells` activation, affect differentiated T cell p
opulations and most importantly decrease disease exacerbation. To this end, we have isolated and characterized two TCRm Abs directed against MOG 35-55/ HLA-DR2 epitopes. These TCRm Abs can obtain their function via two mechanisms of action: (i) block peptide-MHC interactions between pathogenic T cells and APCs, and (ii) specifically eliminate APCs presenting MS-associated autoantigens by ADCC or CDC. The TCRm Abs exhibit specific inhibition of T cell proliferation in vitro and ex vivo. Moreover, the TCRm Abs were able to mediate specific killing of MOG- presenting APCs. According to these data, antigen-specific TCRm Abs are valuable molecules that may facilitate important studies related to antigen presentation in autoimmunity and contribute to the development of innovative therapeutic and diagnostic agents for treating autoimmune disorders such as MS.
