This proposal is based upon recent data obtained during a visit to the Weizmann Institute, Rehovot, Israel. These data suggested that T lymphocyte lines from different rat strains recognized different regions of the myelin basic protein molecule, and that the recognition pattern was dictated by the antigen presenting cell. The dominant region of BP for each strain was able to stimulate T cell reactivity which induced paralytic disease (EAE) as well as protection from subsequent induction of disease. Because BP may be relevant neuroantigen in human paralytic diseases such as multiple sclerosis (MS), and because responsiveness to regions of BP could be regulated by the major histocompatibility complex (MHC), we propose to evaluate the immunodominant regions of BP in normal volunteers and MS patients in the context of Class II MHC antigens. This evalution will be accomplished by selecting BP specific T cell lines, cloning these lines, and then evaluting responsiveness to purified fragments of BP. The role of Class II MHC antigens will be inferred from HLA-D typing results, by stimulation of T cell clones with antigen presenting cells with partial identity in the HLA-D region, and by inhibition of HLA-DR, DP, and DQ dependent activation of T cell clones. From these data, we hope to determine 1) what regions of human BP stimulate human T cells, 2) the number of immunodominant determinants recognized by each individual, 3) whether the range and distribution of T cell responses differ in normal individuals and MS patients, and 4) whether HLA-D region gene products are associated with T cell recognition of human BP determinants.
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