B-T lymphocyte interactions in experimental autoimmune myasthenia gravis: autoantibody mediated up-regulation of the response of acetylcholine receptor-specific T lymphocytes.
Twenty-six monoclonal antibodies of five different isotypes and reactive against distinct parts (alpha, beta, gamma, delta-subunits) of the nicotinic acetylcholine receptor (AChR) from Torpedo californica were screened for their capacity to enhance activation of AChR-specific CD4+ autoreactive T cells. The T-cell line (LR) used in this study recognized an epitope (98-116) on the alpha-subunit of Torpedo AChR. Four monoclonal antibodies bearing a gamma 2b isotype and recognizing an epitope on the Torpedo AChR alpha-subunit, especially the main immunogenic region (MIR), were able to enhance T-cell activation in a dose-response manner. Four further gamma 2b isotype monoclonal antibodies, recognizing epitopes other than the AChR alpha-subunit, had no effect. Monoclonal antibodies of other isotypes (IgM, IgG1, IgG2a, IgG2c), irrespective of their subunit specificity, were unable to influence the T-cell response. Thus, the enhancement requires a IgG2b isotype, and both the antibody and the T-cell recognize an epitope on the same subunit. We have previously shown that AChR-specific B cells are directly able to present antigen to AChR-specific T-cell lines in a privileged way. The present data demonstrate that B cells are also capable of enhancing indirectly the immunogenicity of autoantigens via their humoral antibodies.
Zhang
Y
Y
Department of Neurology, CHUV, Lausanne, Switzerland.
Tzartos
S
S
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D005260:Female; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D011950:Receptors, Cholinergic