The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia.
We characterize a monoclonal antibody directed against the antigen/Ia receptor of a cloned helper T cell line that induced T cell clone proliferation and T cell clone-dependent B cell proliferation at antibody concentrations as low as 10(-11) M. A Fab fragment of this antibody was not stimulatory, implicating cross-linking of antigen receptors as the primary signal for T cell activation. The Fab fragment inhibited activation of this clone by both allogeneic Ia and antigen plus self-Ia, but not by the nonspecific stimulators concanavalin A and rabbit anti-mouse brain serum. This strongly supports the hypothesis that a single molecule mediates both self-Ia plus antigen and non-self-Ia recognition. This molecule is presumably the disulfide-linked heterodimer comprised of 42,000 mol wt acidic and basic subunits precipitated by this monoclonal antibody. The cell surface and internal precursor forms of this protein are also identified. In addition, the response to allogeneic Ia stimulation was more readily inhibited by the Fab fragment than was the response to antigen plus self-Ia, suggesting that alloreactivity reflects a low affinity interaction with a ligand represented at high frequency on the stimulatory cell.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology / Q000302:isolation & purification; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive; D011232:Chemical Precipitation; D002999:Clone Cells / Q000032:analysis / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology / Q000302:isolation & purification; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D006377:T-Lymphocytes, Helper-Inducer / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments