Sequestration of p56lck by gp120, a Model for TCR Desensitization

Academic Article


  • Ligation of the CD4 receptor by HIV envelope glycoprotein gp120 inhibits T cell activation and signaling through the TCR complex. Recent reports suggest CD4 ligation by gp120 + anti-gp120 Abs uncouples protein tyrosine kinases (PTKs) from the TCR signal-transduction cascade. This finding and other observations led us to hypothesize that the effects of gp120 are mediated through p56 , a PTK noncovalently associated with CD4. To test this hypothesis, we first examined the kinetics of gp120/anti-gp120-induced TCR signaling defects in the Jurkat T cell line. Pretreating cells with gp120/anti-gp120 for 1 to 4 h before stimulation prevented TCR-directed PTK activation. Coincident with TCR desensitization, pretreatment with gp120/anti-gp120 also decreased the amount of p56 that could be immunoprecipitated from the Nonidet P-40 detergent-soluble fraction of cellular lysates, while simultaneously increasing the recovery of p56 from the Nonidet P-40 detergent-insoluble fraction (or cytoskeleton). To assess the potential role of the actin in this process, experiments were conducted in the presence of cytochalasin D. Cytochalasin D restored TCR signaling in cells previously desensitized with gp120/anti-gp120 and prevented translocation of p56 from the Nonidet P-40 detergent-soluble fraction of cell lysates. Furthermore, p56 was found to coimmunoprecipitate with anti-actin. These data suggest that gp120/anti-gp120 may inhibit TCR signaling by sequestering p56 to the cytoskeleton. lck lck lck lck lck lck
  • Published In

    Author List

  • Goldman F; Crabtree J; Hollenback C; Koretzky G
  • Start Page

  • 2017
  • End Page

  • 2024
  • Volume

  • 158
  • Issue

  • 5