Study of antigen receptors and peptide recognition by T cells in multiple sclerosis

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1. To study the T cell receptor (TCR) repertoire in multiple sclerosis (MS), we have introduced a novel clonotype analysis method, single strand conformation polymorphism (SSCP). By using this technique, we analyzed the TCR repertoire in the brain lesions and peripheral blood of MS patients. The following points have emerged : (1) the number of clones infiltrated in the brains is moderately restricted (50-100/lesion), though no special preference for a particular Vbeta gene is noted. (2) myelin basic protein (MBP) 82-102 or proteolipid protein (PLP) 95-116-specific T cells are in vivo expanded and activated in the patients studied. (3) T cells in the peripheral nerves of chronic inflammatory demyelinating polyneuropathy (CIDP) preferentially utilize Vbeta11 gene. These results indicate that a limited number of clones are involved in the development of MS and CIDP,and MBP and PLP are candidate autoantigens for MS.2. It is generally believed that recognition by autoimmune encephalito genic T cells is highly specific for their own encephalito genic epitope. However, we have found that MBP89-101-specific encephalitogenic T cells clones derived from SJL/J mice can corecognize PLP136-150 and PLP95-116 as well. Experiments with alanin substitution analogues showed that I-A^s binding residues appeared to be shared by MBP89-101 and PLP136-150. But TCR contact residues seemed to be different. Thus, it has been concluded that some autoimmune T cells are polyreactive and can have multiple sets of TCR contact sites.