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Related Experiment Videos

CD4 changes conformation upon ligand binding.

G Szabò1, P S Pine, J L Weaver

  • 1Center for Drug Evaluation and Research, FDA, Washington, DC 20204.

Journal of Immunology (Baltimore, Md. : 1950)
|December 11, 1992
PubMed
Summary
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Aurintricarboxylic acid (ATA) unexpectedly disengages bound antibodies like OKT4E from CD4 receptors on human cells. This suggests a new method for immunomodulation by inducing ligand release from antigens.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • CD4 is a crucial co-receptor for T-cell activation and a target for HIV.
  • Aurintricarboxylic acid (ATA) is known to inhibit interactions involving CD4, such as HIV gp120 binding.
  • Monoclonal antibodies (mAbs) like OKT4E bind to specific epitopes on CD4, aiding in cellular analysis and understanding immune responses.

Purpose of the Study:

  • To investigate the effect of ATA on the binding of various mAbs to CD4.
  • To explore the mechanism by which ATA influences mAb-CD4 interactions.
  • To assess the potential of ATA as a novel immunomodulatory agent.

Main Methods:

  • Treatment of human peripheral blood lymphocytes (PBL) and a CD4-positive cell line with ATA.
  • Assessing the disengagement of bound mAbs (OKT4E, anti-Leu 8) using flow cytometry.

Related Experiment Videos

  • Utilizing recombinant soluble CD4 (sCD4) and immobilized OKT4E for binding studies.
  • Employing photobleaching fluorescence resonance energy transfer (pFRET) to detect conformational changes in CD4.

    • Main Results:

    • ATA rapidly disengages the OKT4E mAb from CD4 on PBL and cell lines.
    • Disengagement is specific, with only OKT4E and anti-Leu 8 showing rapid release among 12 tested mAbs.
    • ATA-induced disengagement is prevented by cross-linking OKT4E or blocking the Leu 3a site, but not by gp120.
    • pFRET measurements indicate ATA causes CD4 conformational changes, similar to those induced by gp120 binding, leading to indirect mAb release.

    Conclusions:

    • ATA can induce rapid, indirect disengagement of specific mAbs from CD4 through conformational changes.
    • This phenomenon highlights a potential novel mechanism for immunomodulation by controlling ligand-antigen interactions.
    • The findings offer new insights into CD4 receptor dynamics and antibody binding.