FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation.
Ta1 (CDw26) is a 105-kDa glycoprotein of unknown function whose expression on human T lymphocytes is strongly correlated with activation and proliferation. The subset of peripheral blood T cells expressing Ta1 includes the principal responsive population to proliferative stimulation by recall antigens as well as monoclonal antibodies directed to the CD3/T cell receptor complex and the CD2 (T11) molecule. We now show that the Ta1 molecule is itself an alternate mediator of human T lymphocyte activation. T cell clones were induced to proliferate and exert their cytolytic effector function by anti-Ta1 monoclonal antibodies in the presence of Fc-receptor-positive accessory or target cells. Resting T cells from peripheral blood were also activated to proliferate by anti-Ta1, but only if both Fc-receptor-positive accessory cells and exogenous IL-2 were present. Anti-Ta1 antibodies induced increased expression of IL-2 receptors on purified T cells under these conditions. Activation via Ta1 was shown to be functionally interconnected to CD3/T cell receptor activation mechanisms, because modulation of the CD3/T cell receptor complex inhibited anti-Ta1-mediated cytolysis without affecting Ta1 surface expression. While demonstrating that the CDw26 antigen-mediated pathway of activation is not dependent on one unique epitope, our results suggest that the Ta1 glycoprotein can mediate T cell activation directly, suggesting that it may be associated with an important cellular component of the human T cell regulatory network.
Dang
N H
NH
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Hafler
D A
DA
Schlossman
S F
SF
Breitmeyer
J B
JB
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000502:physiology; D017252:CD3 Complex; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7