A serine phosphatase is involved in CD2-mediated activation of human T lymphocytes and natural killer cells.
We investigated early activation events after T cell triggering via the Ag receptor (TCR/CD3) complex as compared to activation via the CD2 surface molecule. To this end, resting peripheral human T lymphocytes were preincubated with 32P-orthophosphate and subsequently exposed to mitogenic mAb directed at either TCR/CD3 or CD2 for varying time periods. Cells were lysed and postnuclear lysates subjected to two-dimensional-gel electrophoresis (IEF and SDS-PAGE). As early as 10 min after stimulation through CD2, dephosphorylation of a cytosolic 19-kDa protein was observed. In contrast, this protein remained phosphorylated in unstimulated as well as CD3 activated T cells. Phosphoprotein (pp) 19 dephosphorylation was transient because, at later time points (2-4 h) after CD2 triggering, this protein was phosphorylated again. Phosphoaminoacid analysis indicated that pp19 is dephosphorylated on serine residues. Identical results were obtained using a CD2+ but TCR/CD3- human NK cell clone indicating that pp19 dephosphorylation occurs independent of surface expression of a TCR/CD3 complex. These data show that, in addition to protein phosphorylation events, serine dephosphorylation is involved in T cell triggering. More important, a selective signaling mechanism appears to be linked to T cell activation through the CD2 pathway.
Abteilung Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
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Bader
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Meuer
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D015180:Electrophoresis, Gel, Two-Dimensional; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D004988:Ethers, Cyclic; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D019319:Okadaic Acid; D007371:Interferon-gamma; D010749:Phosphoprotein Phosphatases