Defective TCR-mediated signaling in anergic T cells.
Extrathymic T cell tolerance to Ags can be achieved through clonal deletion by activation-induced programmed cell death as well as by functional unresponsiveness (anergy) of Ag reactive-T cells. Previous studies demonstrated that in vivo administration of staphylococcal enterotoxin B (SEB) induces SEB-specific T cell anergy. To investigate the molecular mechanisms of T cell anergy, we analyzed the TCR-mediated signal transduction in normal and anergic T cells. Anergic T cells exhibited impaired protein tyrosine phosphorylation on TCR-mediated stimulation. The altered tyrosine phosphorylation in anergic T cells may be caused by a defect in tyrosine phosphorylation of TCR zeta-chain and its subsequent association with ZAP-70 tyrosine kinase. Our data demonstrated that TCR zeta-chain phosphorylation and its sequential interaction with ZAP-70 are essential for the initiation of TCR-mediated signal transduction.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Kawabe
Y
Y
Tsukada
T
T
Ichinose
Y
Y
Nagataki
S
S
Ochi
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051746:ZAP-70 Protein-Tyrosine Kinase
D004768:Enterotoxins; D007376:Interleukin-2; D007476:Ionophores; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C054979:antigen T cell receptor, zeta chain; C031818:enterotoxin B, staphylococcal; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium