Dephosphorylation of pp19: a common second signal for human T cell activation mediated through different accessory molecules.
Accessory molecules are thought to provide essential regulatory signals for T cell activation. In order to identify specific intracellular events linked to triggering through accessory surface receptors, mAbs against CD2, CD3, CD4, and CD8 were employed to activate resting human T lymphocytes in vitro. Subsequently, intracellular phosphorylation of phosphoprotein (pp) 19, a recently identified substrate of a serine phosphatase involved in CD2 mediated T cell triggering, as well as functional parameters (responsiveness to IL-6, production of IL-2 and IFN-gamma) were determined. As in responses to CD2 mAbs, cross-linking of CD4 and/or CD8 to the TCR-CD3 complex but not CD3 cross-linking alone promoted pp19 dephosphorylation. This early event was in all cases followed by particular late functional responses, i.e. induction of IL-6 responsiveness and secretion of IL-2. In marked contrast, no relationship was found between pp19 dephosphorylation and IFN-gamma production. Taken together, a common intracellular pathway appears to exist in which signals mediated through CD2, CD4, and CD8 merge to promote monokine responsiveness and IL-2 production in human T cells. Dephosphorylation of pp19 thus appears to represent a process which is linked to critical 'second signals' involved in the generation of antigen induced T cell responses.
Samstag
Y
Y
Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Henning
S W
SW
Bader
A
A
Meuer
S C
SC
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D007376:Interleukin-2; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma