Identification and functional characterization of two distinct epitopes on the human T cell surface protein Tp50.
The structural and functional domains of Tp50, the human T lymphocyte surface protein associated with the E rosette receptor, were probed with the use of two murine monoclonal antibodies. Lysostripping, immune precipitation, and competitive binding experiments demonstrated that antibodies 9.6 and 35.1 bind to Tp50 epitopes in close proximity. In functional studies, both antibodies caused a similar degree of antigenic modulation, inhibited T cell proliferative responses, and inhibited cytotoxic T lymphocyte function without affecting cells that mediate antibody-dependent cell-mediated cytotoxicity. The antibodies were strikingly different, however, in that antibody 9.6 inhibited E rosette formation and natural killer cell-mediated lysis, whereas antibody 35.1 did not. These results could not be ascribed to differences in antibody class or binding characteristics, because Scatchard analysis demonstrated that these two IgG2a antibodies have comparable avidity and that T cells bind each antibody in equivalent amounts. The differential binding of antibodies 9.6 and 35.1 to T cells from nonhuman primates further supports the interpretation that the differences between the antibodies in their effects on E rosette formation and natural killer function stem from the fact that they bind to distinct epitopes of Tp50. The implications of these findings for understanding the functions of Tp50 molecules are discussed.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology*; D010215:Papio; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000939:Epitopes; D008565:Membrane Proteins