Generation of acetylcholine receptor-specific human T cell lines using heterobifunctional antibody-targeted antigen presentation.
Characterizing AChR-specific T lymphocyte clones is an important step towards the ability to induce antigen-specific tolerance in myasthenia gravis (MG). However, the limited supply of relatively inefficient autologous antigen presenting cells (APCs) makes establishing AChR-specific T lymphocyte lines difficult. In this study we targeted AChR to autologous surface IgM+ (sIgM+) APCs using heterobifunctional antibodies (bi-Ab) consisting of anti-sIgM linked to anti-AChR antibodies. FACScan analysis and whole cell-based radioimmunoassay (RIA) showed binding of bi-Ab/AChR conjugates to sIgM+ APCs. Using antigen targeting, AChR-presentation to a well-characterized AChR-specific T cell clone, and to T cell lines raised de novo from MG thymocytes, was improved. Thus, antigen targeting using bi-Ab improved the efficiency of presentation of the scarce autoantigen AChR, suggesting that this method might allow the use of relatively impure antigen preparations and normally inefficient non-antigen-specific APCs, including those which can be immortalized, to accelerate the characterization of the AChR epitopes recognized by pathogenic T helper lymphocytes.
Wang
D
D
Department of Clinical Neurological Sciences and Microbiology and Immunology, University Campus, London Health Sciences Centre, University of Western Ontario, Canada.
Nicolle
M W
MW
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D018033:Antibodies, Bispecific / Q000276:immunology*; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002461:Cell Line, Transformed / Q000276:immunology; D002999:Clone Cells; D004854:Herpesvirus 4, Human; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D013934:Thymectomy; D013945:Thymoma / Q000276:immunology / Q000473:pathology / Q000601:surgery; D013953:Thymus Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery; D014101:Torpedo / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D018033:Antibodies, Bispecific; D001324:Autoantigens; D007075:Immunoglobulin M; D007518:Isoantibodies; D011947:Receptors, Antigen, B-Cell; D011950:Receptors, Cholinergic; C044203:anti-IgM