Several mechanisms have been implicated in the activation and expansion of myelin-specific T cells in multiple sclerosis, a presumed autoimmune disease of the central nervous system. In this article, we will review the mechanisms of molecular mimicry whereby myelin-specific T lymphocytes may be activated by foreign antigens. Recent studies from our laboratory have documented an unexpected flexibility of T cell receptor recognition and demonstrated that sequence homology is not a requirement for cross-recognition. Using synthetic combinatorial peptide libraries, it was possible to identify the entire spectrum of molecular mimics for T cell clones. This approach may prove useful for the development of antigen-specific therapies and vaccines.
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