Circulating regulatory anti-T cell receptor antibodies in patients with myasthenia gravis.
Serum anti-T cell receptor (TCR) Ab's are involved in immune regulation directed against pathogenic T cells in experimental models of autoimmune diseases. Our identification of a dominant T cell population expressing the Vbeta5.1 TCR gene (TCRBV5-1), which is responsible for the production of pathogenic anti-acetylcholine receptor (AChR) autoantibodies in HLA-DR3 patients with early-onset myasthenia gravis (EOMG), prompted us to explore the occurrence, reactivity, and regulatory role of anti-TCR Ab's in EOMG patients and disease controls with clearly defined other autoantibodies. In the absence of prior vaccination against the TCR, EOMG patients had elevated anti-Vbeta5.1 Ab's of the IgG class. This increase was restricted largely to EOMG cases with HLA-DR3 and with less severe disease, and it predicted clinical improvement in follow-up studies. EOMG patient sera containing anti-TCR Ab's bound specifically the native TCR on intact Vbeta5.1-expressing cells and specifically inhibited the proliferation and IFN-gamma production of purified Vbeta5.1-expressing cells to alloantigens in mixed lymphocyte reaction and the proliferation of a Vbeta5.1-expressing T cell clone to an AChR peptide, indicating a regulatory function for these Ab's. This evidence of spontaneously active anti-Vbeta5.1 Ab's in EOMG patients suggests dynamic protective immune regulation directed against the excess of pathogenic Vbeta5.1-expressing T cells. Though not sufficient to prevent a chronic, exacerbated autoimmune process, it might be boosted using a TCR peptide as vaccine.
Jambou
Florence
F
Centre National de la Recherche Scientifique (CNRS) Unité de Recherche (UMR) 8078 - Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
Zhang
Wei
W
Menestrier
Monique
M
Klingel-Schmitt
Isabelle
I
Michel
Olivier
O
Caillat-Zucman
Sophie
S
Aissaoui
Abderrahim
A
Landemarre
Ludovic
L
Berrih-Aknin
Sonia
S
Cohen-Kaminsky
Sylvia
S
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D002455:Cell Division; D004306:Dose-Response Relationship, Immunologic; D004576:Electromyography; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007700:Kinetics; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors; D014612:Vaccines / Q000737:chemistry
D000906:Antibodies; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D014612:Vaccines