title: The T11 (CD2) molecule is functionally linked to the T3/Ti T cell receptor in the majority of T cells.
abstract: Most mature human T lymphocytes express both the multichain T3 (CD3)/Ti T cell receptor for antigen (TCR), and the biochemically distinct 55-kDa T11 (CD2) glycoprotein. Stimulating the T11 molecule causes profound T cell proliferation and functional activation in vitro, but the relationship of T11-mediated activation to antigenic stimulation of T lymphocytes in vivo remains unknown. We now present evidence that T11 function is directly linked to TCR components in T3/Ti+ T11+ human T cells. First, we found that stimulating peripheral blood T cells with the mitogenic combination of anti-T11(2) cells with the mitogenic combination of anti-T11(2) plus anti-T11(3) monoclonal antibodies caused the phosphorylation of TCR T3 chains. The predominance of T3-gamma-phosphorylation that occurred in anti-T11(2) plus anti-T11(3)-treated T cells is similar to the pattern previously observed in antigen-stimulated T cell clones. Second, T11 function depended upon concurrent cell-surface expression of the TCR. Thus, when peripheral blood T cells were deprived of cell surface T3/Ti by anti-T3 modulation, anti-T11(2) plus anti-T11(3)-induced mitogenesis and transmembrane signal generation in the form of calcium mobilization were inhibited. The mechanism of TCR-T11 interdependence was investigated in a series of TCR-deficient variants of a T cell lymphoblastoid cell line. T3/Ti negative variants expressed cell surface T11, but anti-T11(2) plus anti-T11(3) failed to cause detectable calcium mobilization. The TCR-deficient variants also failed to express T11(3) activation epitopes after incubation with anti-T11(2) antibodies, suggesting that T11(3) expression is an essential and TCR-dependent intermediate in the T11 activation mechanism in these cells. Taken together, our results suggest that T11 function depends upon cell-surface expression of TCR in many T3/Ti+ T11+ T lymphocytes, and T11-mediated activation is intimately interconnected with TCR activation mechanisms. A model in which stimulating signals delivered via T11 may be a part of antigenic activation of T lymphocytes is presented.
mesh_terms: D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology; D017252:CD3 Complex; D004705:Endocytosis; D000939:Epitopes; D006801:Humans; D007152:Immunologic Capping; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D013755:Tetradecanoylphorbol Acetate