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From the Neuroimmunology Branch (Drs. Hemmer, Vergelli, McFarland, and Martin and L. Tranquill), NINDS, National Institutes of Health, Bethesda, MD; Department of Neurology (Dr. Martin), Tübingen University Medical School, Tübingen, Germany; and Neurocrine Biosciences, Inc.(Drs. Conlon and Ling), San Diego, CA.
Address correspondence and reprint requests to Dr. R. Martin, Neuroimmunology Branch, NINDS, NIH, Building 10, Room 5B-16, 10 Center DR MSC 1400, Bethesda, MD 20892-1400.
Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, and myelin proteins are the most likely candidate autoantigens. Based on experiments performed in experimental allergic encephalomyelitis(EAE), innovative immunotherapies have been developed that target either the specific trimolecular complex of encephalitogenic T cells, consisting of T-cell receptor (TCR), major histocompatibility complex (MHC; HLA in humans) class II molecule, and autoantigenic peptide, or the effector functions of these cells. To provide the basis for the transfer of these specific immunotherapies to MS, we extensively characterized the human T-cell response to one major myelin epitope, the myelin basic protein peptide(83-99). We analyzed restriction element, TCR usage and affinity, fine specificity, cytokine production, cytolytic activity, and expression of surface molecules on 41 T-cell clones (TCCs) derived from MS patients and normal controls. We demonstrate a high degree of complexity of recognition patterns as well as of functional phenotypes among T cells responding to the same epitope. In contrast to results from animal models, these findings indicate that the design of epitope-based specific immunotherapies for MS is more difficult than previously thought.
Supported in part by Small Business Innovation Research Grant from the Department of Health and Human Services, Public Health Service. B. Hemmer is a post-doctoral (He 2386/1-2) and R. Martin a Heisenberg Fellow of the Deutsche Forschungsgemeinschaft (Ma 965/4-1).
Received November 25, 1996. Accepted in final form May 2, 1997.
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