Gene Activating and Proapoptotic Potential Are Independent Properties of Different CD4 Epitopes

Mol Immunol. 1997 Mar;34(4):287-96. doi: 10.1016/s0161-5890(97)00050-3.

Abstract

CD4 engagement triggers an early signaling cascade which initiates late events such as transcription factor activation. The outcome of CD4 engagement is T-cell commitment to alternative, dramatically different fates, such as activation and apoptosis. We have tested a panel of anti-CD4 mAbs specific for different CD4 epitopes, as well as HIV-1 gp120, for the capacity to activate crucial early events such as enhancement of p56(lck) kinase activity and Shc phosphorylation. The same CD4 epitopes were characterized for their capacity both to deliver a gene activating signal and to program T-cells to activation dependent death. No correlation could be found between capacity of specific CD4 epitopes to deliver a gene activating signal and capacity to prime T-cells to apoptosis, suggesting that gene activating and proapoptotic potential are independent functions of CD4 epitopes. Furthermore, while triggering of the calcium pathway appears critical in NF-AT activation, optimal p56(lck) activation and Shc phosphorylation might be required for initiation of the apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / physiology
  • Apoptosis / immunology*
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD4 Antigens / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epitopes / genetics
  • Epitopes / immunology
  • Epitopes / physiology*
  • Gene Expression Regulation / immunology*
  • HIV Envelope Protein gp120 / pharmacology
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / genetics
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Signal Transduction / immunology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation / immunology

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • DNA-Binding Proteins
  • Epitopes
  • HIV Envelope Protein gp120
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors