Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis.
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-gamma 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 10(5) 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-gamma can be important for the pathogenesis of MS.
Department of Neurology Karolinska Institutet, Huddinge University Hospital, Sweden.
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T
Olsson
J
J
Sun
J
J
Hillert
B
B
Höjeberg
H P
HP
Ekre
G
G
Andersson
O
O
Olerup
H
H
Link
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000939:Epitopes; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D004676:Myelin Basic Protein; D010455:Peptides; D007371:Interferon-gamma