Binding of the hepatitis C virus (HCV) envelope protein E2 to CD81 provides a costimulatory signal for human T cells. This phenomenon may play a role in liver damage and autoimmune manifestations associated with HCV infection. Here we show that cross-linking of CD81 by HCV E2 induced a calcium flux in T cells that depends on Lck since it was blocked by PP1 and absent in Lck-deficient Jurkat T cells. In wild-type Jurkat cells, Lck was activated by CD81 cross-linking, and CD81, like Lck, was found in lipid rafts. Indeed, the integrity of the raft compartment was required for the induction of a calcium flux by E2, since methyl- g - cyclodextrin abolished this response. A requirement for TCR/CD3 expression was indicated by the absence of a calcium flux following E2 stimulation of TCR/CD3-deficient Jurkat cells. CD81 cross-linking increased and prolonged the anti-CD3-induced tyrosine phosphorylation of TCR ́ and of other proteins, indicating that the CD81-mediated signal converges with the TCR/CD3 signaling cascade at its most upstream step. In conclusion, we propose that the costimulatory effects of HCV E2 on T cells depend on CD81 cross-linking that activates Lck through raft aggregation and thus leads to enhanced TCR signaling.
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|Titolo:||T cell costimulation by the hepatitis C virus envelope protein E2 binding to CD81 is mediated by Lck|
|Rivista:||EUROPEAN JOURNAL OF IMMUNOLOGY|
|Citazione:||Soldaini, E., Wack, A., Doro, U., Nuti, S., Ulivieri, C., Baldari, C., et al. (2003). T cell costimulation by the hepatitis C virus envelope protein E2 binding to CD81 is mediated by Lck. EUROPEAN JOURNAL OF IMMUNOLOGY, 33(2), 455-464.|
|Appare nelle tipologie:||1.1 Articolo in rivista|