Signal transduction through the T cell receptor-CD3 complex. Evidence for heterogeneity in receptor coupling.
T cell receptor-CD3 complex (TCR-CD3)-mediated signal transduction was analyzed in HPB-ALL and Jurkat T cell lines. Both cell lines express high levels of TCR-CD3 complex on the cell surface, but provide different model systems for TCR-CD3 signaling in T cells. Jurkat responds with both inositol phosphate generation and intracellular Ca2+ mobilization after triggering of TCR-CD3, whereas TCR-CD3 triggering of HPB-ALL induces Ca2+ mobilization without detectable inositol phosphate generation. By employing a permeabilized cell system, we show that the HPB-ALL line expressed normal levels of Ca2(+)-induced phospholipase C activity. However, the TCR-CD3 on this cell line seems to be uncoupled from phospholipase C activation. In agreement with this result we also show, by analysis of protein kinase C-dependent phosphorylation of three distinct substrates, that TCR-CD3 in HPB-ALL is apparently uncoupled from protein kinase C activation. These findings may have implications for understanding signal-transducing pathways in T cells at various stages of differentiation.
Brattsand
G
G
Unit of Applied Cell and Molecular Biology, University of Umeå, Sweden.
Cantrell
D A
DA
Ward
S
S
Ivars
F
F
Gullberg
M
M
D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D004789:Enzyme Activation; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D011994:Recombinant Proteins; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium