Multiple Sclerosis (MS) is a serious and ofter disabling disorder which affects approximately 250,000 individuals in this country. Experimental allergic encephalomyelitie (EAE) is an experimental autoimmune disease which is often proposed as a model for the MS. Therefore, it is postulated that autoimmunity ply some role in the pathogenesis of MS. EAE may be induced in susceptible animals by immunization with myelin antigens including myelin basic protein (MBP), proteolipid protein, and patients or control subjects. Whether other myelin antigens are recognized by the lymphocytes from MS patients or control subjects is one question to be addressed by this research. The second question concerns the fine specificity and the cytotoxic potential of these T cells. The basic questions to be studied in this proposed research include; 1) Are there myelin antigens other than MBP which are recognized by T- lymphocytes isolated from MS patients or control subjects, 2) Following cloning of T-cells reactive with whole myelin, will a majority of the clones respond to any particular """"""""immunodominant"""""""" antigen, and 3) Will these T cells by cytotoxic for any particular MBP epitope. The techniques used will include: 1) Establishment of T- lymphocyte clones recognizing purified myelin, MBP, proteolytic fragments and synthetic peptides of MBP, and control antigens. 2) Determining the specificity and cytotoxic activity of these cells. A better understanding of the potential autoimmune target antigens in myelin and the T cells which recognize these may aid in understanding the pathogenesis of human demyelination diseases.
