Selective activation of gamma/delta + T cell clones by single anti-CD2 antibodies.
The CD2 antigen is the target for an "alternative" T cell activation pathway. Numerous studies have demonstrated that pairs of monoclonal antibodies (mAbs) directed toward two different epitopes are required for activation of T cell receptor (TCR)-alpha/beta + T cells via CD2. We have now explored the activation of human TCR-gamma/delta + T cell clones by a panel of anti-CD2 mAbs directed against the sheep erythrocyte-binding (T11.1) epitope of CD2. Seven of seven gamma/delta + clones expressing different molecular forms of the TCR-gamma/delta responded to stimulation by a single anti-CD2 mAb (OKT11, 9E8, BW0110, M-T910) with IL-2 secretion and/or proliferation. Immobilization of anti-CD2 mAbs in microculture plates was essential for activation of gamma/delta + clones, which occurred in the absence of feeder cells. In addition to interleukin 2 (IL-2) production and proliferation, anti-CD2 mAbs also triggered cytotoxic effector activity in gamma/delta + clones as measured against FcR+ P815 target cells. In contrast to gamma/delta + clones (but in line with established data), none of five CD4+ or CD8+ TCR-alpha/beta + clones were activated by any of the tested individual anti-CD2 mAbs. Taken together, our results reveal a striking difference between cloned gamma/delta + and alpha/beta + T cells in that gamma/delta + T cells are selectively activated by a single anti-CD2 (T11.1) mAb, without need for the simultaneous signal of a second anti-CD2 mAb directed against another (T11.2 or T11.3) CD2 epitope.
Institut für Immunologie, Universität Heidelberg, Federal Republic of Germany.
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Wesselborg
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Janssen
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Pechhold
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Kabelitz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011961:Receptors, Fc / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D000939:Epitopes; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011961:Receptors, Fc; D011971:Receptors, Immunologic