Clonal analysis of antigen-specific interactions between T cells and genetically engineered B cells.
In order to investigate T cell-B cell interactions we constructed monoclonal, antigen-specific T- and B-cell populations. The Ia+ B-cell lymphoma A20-2J was transfected with trinitrophenyl (TNP)-specific heavy (mu) and light (kappa) chain Ig genes. A hapten-carrier complex (TNP-keyhole limpet hemocyanin (KLH)) bound to the surface Ig expressed on the transfectant and was presented to carrier-specific T-cell hybridoma clones at markedly low doses of antigen (0.01 microgram/ml) and in an Ia-restricted fashion. Two responses were elicited in the responding T-cell clones: (i) high levels of IL-2 secretion (320 units/ml), and (ii) cytotoxicity directed against the antigen-presenting B cell. This cytotoxicity was inhibited by D-mannose and was directed against innocent bystander cells, unlike cytotoxicity mediated by NK cells or alloreactive cytotoxic T lymphocyte. Helper and cytotoxic functions were often present in different T-cell hybridomas but some clones exhibited both activities. One representative T-cell hybridoma exhibited strong helper function for TNP-primed splenic B cells as detected in a plaque-forming cell assay, but was cytotoxic toward antigen-presenting B cells. Such monoclonal assay systems for studying cognate interactions of heterogeneous T cells and specific antigen-presenting cells will provide us with valuable new approaches for the study of antigen-specific T-cell regulation of B-cell activation in immune responses.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006433:Hemocyanins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008211:Lymphocyte Cooperation; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D014301:Trinitrobenzenes; D006433:Hemocyanins