Antigen-specific and polyclonal immunoglobulin production induced by a cloned tetanus toxoid-specific T cell line.
This report describes the isolation and the phenotypic and functional characterization of a cloned, IL 2 dependent, TT-specific human helper T cell line (TCL), designated 1A1. 1A1 was derived by limiting dilution culture of a bulk IL 2-dependent TCL that was found to contain both TT and trinitrophenyl (TNP) altered self-reactive T cells. Specifically, 1A1 represents the outgrowth of one well of a microwell cloning plate initially seeded at 1 TCL/well, from which less than 4% (3/96) wells grew. Phenotypic analysis, utilizing a battery of monoclonal antibodies, demonstrates that all 1A1 cells are T cells belonging to a stable and discrete T cell subset: T3+, T4+, T17+, T8-. In proliferative assay, 1A1 responds specifically to TT but not to other soluble antigens against which the donor is sensitized, a panel of allogeneic stimulators, nor to TNP-modified-self. Moreover, 1A1 is HLA-DRw-restricted, proliferating only to TT in association with DRw3+ antigen-presenting cells. Of greater interest is the observation that 1A1 is an antigen-specific helper T cell line. Thus, by utilizing ELISA systems to quantitate class-specific immunoglobulin and antigen-specific antibody, it was determined that co-culture of autologous B cells, 1A1 cells, and a low concentration (1 to 10 ng/ml) of TT results in an IgG response that is predominantly, if not exclusively, antigen-specific antibody. In contrast, the presence of high concentrations of TT (4 micrograms/ml) triggers a polyclonal immunoglobulin response comprised of IgM with a small IgG component that is essentially devoid of anti-TT antibody. These results demonstrate that depending on the mechanism of activation, a cloned antigen-specific helper T cell line can mediate antigen-specific or polyclonal help for autologous B cells.
D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000032:analysis* / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*
D000907:Antibodies, Bacterial; D000939:Epitopes; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D013745:Tetanus Toxoid