Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells

Andreas Wack, Elisabetta Soldaini, Chien Te K. Tseng, Sandra Nuti, Gary R. Klimpel, Sergio Abrignani

Research output: Contribution to journalArticle

131 Scopus citations


Chronic hepatitis C virus (HCV) infection frequently develops into liver disease and is accompanied by extra-hepatic autoimmune manifestations. The tetraspanin CD81 is a putative HCV receptor as it binds the E2 envelope glycoprotein of HCV and bona fide HCV particles. Here we show that HCV E2 binding to CD81 on human cells in vitro lowers the threshold for IL-2 receptor alpha expression and IL-2 production, resulting in strongly increased T cell proliferation. HCV E2-induced co-stimulation also enhances the production of IFN-γ and IL-4 and causes increased TCR down-regulation. This suggests that binding of HCV particles to CD81 on T cells in vivo may lead to activation by otherwise suboptimal stimuli. Therefore, co-stimulation of autoreactive T cells by HCV may contribute to liver damage and autoimmune phenomena observed in HCV infection.

Original languageEnglish (US)
Pages (from-to)166-175
Number of pages10
JournalEuropean Journal of Immunology
Issue number1
StatePublished - Feb 5 2001



  • Autoimmunity
  • Co-stimulation
  • Hepatitis C virus
  • Human T lymphocyte
  • Tetraspanin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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