T cell responses to D-penicillamine in drug-induced myasthenia gravis: recognition of modified DR1:peptide complexes.
The anti-rheumatoid drug D-penicillamine (D-pen) has a reactive sulfhydryl group capable of modifying self antigens, and can provoke typical autoantibody-mediated myasthenia gravis (MG), especially in DR1+ individuals. We have selected T cell clones from one such patient that were highly specific for D-pen but not its L-isomer or D-cysteine. Moreover, they were restricted to HLA-DR1, had a Th1 phenotype and used TCR V alpha4.1, V beta6.1. They responded well to blood mononuclear cells prepulsed with D-pen either in the absence of serum or after chloroquine treatment, but not to autologous D-pen-pulsed B cell lines. Thus, D-pen may directly couple to distinctive peptides resident in surface DR1 molecules on circulating macrophages or dendritic cells.
Neurosciences Group, Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, UK.
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M
Hill
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P
Moss
P
P
Wordsworth
J
J
Newsom-Davis
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N
Willcox
D000368:Aged; D000595:Amino Acid Sequence; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000276:immunology; D000939:Epitopes; D005260:Female; D015798:HLA-DR1 Antigen / Q000032:analysis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000139:chemically induced / Q000276:immunology*; D010396:Penicillamine / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013936:Thymidine / Q000494:pharmacology; D014316:Tritium
D018501:Antirheumatic Agents; D001798:Blood Proteins; D017252:CD3 Complex; D000939:Epitopes; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014316:Tritium; D002738:Chloroquine; D010396:Penicillamine; D013936:Thymidine