Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis

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Abstract
Myelin basic protein (MBP)-autoreactive T cells have a crucial pathogenetic role in experimental allergic encephalomyelitis (EAE) and certain MBP epitopes may be immunodominantly recognized. The heterogeneity and quantity of the T cell response to different epitopes of MBP in multiple sclerosis (MS) and non-MS controls is not so clearly defined. We now study T cell reactivity to six different peptides of MBP in MS compared to controls in short-term cultures of blood mononuclear cells by measuring numbers of T cells that secrete interferon-γ in response to antigen. In comparison with controls, MS patients showed dramatically increased numbers of MBP peptide-reactive T cells with mean values varying between 10.4 and 22.5 per 105 blood mononuclear cells. Among those MBP peptides examined (amino acid 1–20, 63–88, 89–101, 96–118, 110–128 and 148–165), no single peptide is preferentially recognized. Neither is any preferential response apparent after subdivision of the MS patients according to their HLA-DR genotype. Our findings suggest that a quantitative increase of a broad repertoire of myelin-autoreactive T cells with capacity to secrete IFN-γ can be important for the pathogenesis of MS.