Preferential survival of an MBP-specific T cell clone in an HLA-DR2 multiple sclerosis patient.
Anti-myelin basic protein (MBP) autoreactive T cells play a key role in the pathogenesis of multiple sclerosis. Thus, we applied the Immunoscope strategy to cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBLs) of an HLA-DR2 patient. Both compartments showed major expansion for the V(beta)13S5 chain, which was associated in peripheral blood with significant proliferation of PBLs in response to MBP and the 84-102 HLA-DR2-restricted peptide. Sequencing revealed a unique nucleotide sequence in the CSF that gives rise to the amino acid sequence V(beta)13S5-RPGQGDQETQ-J(beta)2.5 if translated. This CDR3 sequence had already been reported to be reactive against the 84-102 peptide. This specific sequence was not detected in PBLs on day 0, whereas it was readily detectable on day 6 culture samples. Thus, cell culture may lead to enrichment in a T cell clone identified as autoreactive.
Service de Neurovirologie, CEA, CRSSA, EPHE, Fontenay-aux-Roses, France.
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Démoulins
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Naccache
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Clayette
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Musette
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Bequet
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Gachelin
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Dormont
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology*; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D015802:HLA-DR2 Antigen; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta