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Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers
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Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers

Published on: March 6, 2009

Understanding the CD4 molecule: surface expression and function

W J Morrison1, H Offner, A A Vandenbark

  • 1Neuroimmunology Research Laboratory, Veterans Administration Medical Center, Portland, OR 97207.

Journal of Neuroscience Research
|May 1, 1994
PubMed

Insights

Selective CD4 molecule modulation on T cells blocks HIV infectivity while enhancing T cell receptor (TCR) function. This suggests distinct roles for CD4 in viral entry and immune response, impacting HIV-1 infection strategies.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • The CD4 glycoprotein is crucial for T cell receptor (TCR) mediated antigen recognition and serves as a receptor for HIV.
  • Both TCR activation and HIV infectivity are inhibited by anti-CD4 antibodies.
  • Previous studies indicated that CD4 modulation affects both viral entry and T cell function.

Purpose of the Study:

  • To investigate the distinct roles of CD4 surface expression in TCR function and HIV infectivity.
  • To explore mechanisms by which CD4 modulation influences T cell activation and viral entry.

Main Methods:

  • Selective CD4 down-modulation using gangliosides (GM1).
  • Intracellular delivery of CD4 mRNA-antisense oligodeoxynucleotides (ODN) to block CD4 synthesis.
  • Analysis of TCR function following CD4 modulation.
  • Assessment of HIV infectivity after CD4 modulation.

Main Results:

  • Ganglioside-mediated CD4 modulation blocked HIV infectivity but enhanced TCR function.
  • Antisense ODN-mediated inhibition of CD4 synthesis also enhanced TCR function.
  • These distinct CD4 modulation methods converged on enhanced antigen-stimulated TCR function.
  • CD4 antagonism by antibodies or protein kinase C activity reduced CD4 function.

Conclusions:

  • Selective removal of surface CD4 enhances TCR-mediated T cell activation.
  • CD4's role in HIV infectivity is separable from its role in TCR function.
  • These findings redefine CD4's contribution to T cell activation and suggest a role for CD4 subtypes in HIV-1 infection.

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