Activation of T lymphocytes by cross-linking of glycophospholipid-anchored Thy-1 mobilizes separate pools of intracellular second messengers to those induced by the antigen-receptor/CD3 complex.
T cells can be activated, not only by the conventional (antigen-receptor/CD3 complex) route, but also by cross-linking any one of their lipid-anchored surface glycoproteins. We have compared early transmembrane signalling events mediated through CD3 with those mediated through Thy-1, a lipid-linked surface glycoprotein, on the human lymphoid cell line Jurkat and transfectants expressing higher levels of Thy-1. Cross-linking of Thy-1 causes immediate phosphatidylinositol (PI) turnover and an influx of extracellular Ca2+, while releasing very little Ca2+ from intracellular stores. CD3 activation, on the other hand, causes PI turnover which releases intracellular Ca2+, and only secondarily induces an influx of extracellular ions. The Thy-1 response is detectable at very low levels of surface Thy-1, and is not mimicked by enzymatic removal of lipid-linked proteins from the cell surface. The Thy-1-induced Ca2+ influx is more sensitive to L channel blockers than the CD3-mediated flux. These results indicate that the initial stages of Thy-1-mediated activation involve the rapid and extensive mobilization of the intracellular second messengers, PI and Ca2+, by mechanisms separate to those activated by the antigen-receptor/CD3 complex.
Norman and Sadie Lee Research Centre, National Institute for Medical Research, Mill Hill, London, U.K.
E
E
Barboni
A M
AM
Gormley
F B
FB
Pliego Rivero
M
M
Vidal
R J
RJ
Morris
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015290:Second Messenger Systems / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D006017:Glycolipids; D010716:Phosphatidylinositols; D010743:Phospholipids; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D002118:Calcium